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The coronavirus disease-19 (COVID-19) caused by the SARS-CoV-2 virus, is now an ongoing pandemic. First detected in December 2019 at Wuhan, China, this disease has now spread to all parts of the world. COVID-19 may affect anyone, without regard for age, sex, or underlying disease condition. Patients with benign or malignant diseases when affected, usually have a more severe outcome than people without comorbidities. Increasing one’s immunity by vaccination against COVID-19 will help to improve the disease outcomes of COVID-19 in patients who already have some underlying disease. The live-attenuated or killed and recombinant viral protein vaccines currently available can elicit both humoral and cellular immunities. However, in immunocompromised patients (either due to the disease pathology or treatment-related immunosuppression), immune response may not be as effective as expected. Depending on the underlying disease pathogenesis, the patient may not be able to mount an adequate immune response post-vaccination. However, in view of the severe risks posed by COVID-19 disease, vaccination is of utmost importance. This review aims at understanding the importance of SARS-CoV-2 vaccination in patients with hematological disorders, and also aims to understand the side effects which arise post-SARS-CoV-2 vaccination. We have tried to ascertain the best way to vaccinate patients with hematological disorders.

Deferiprone (DFP) and deferasirox (DFX) are the most well-known, efficacious and safe chelators to reduce the serum ferritin (SF) level in multi transfused thalassemic children, although there are few reports available for assessing the efficacy between DFP and DFX. We compared the efficacy of DFP vs. DFX as iron chelating drugs in β-thalassemia major (β-TM) patients. Pediatric patients diagnosed to carry β-TM, aged between 2 and 10 years, were recruited. A suitable data collection form and questionnaire were used. Paired and unpaired t-tests were used to compare the safety and efficacy of the chelating drugs DFP and DFX. The mean SF level at the 12th month was found to be 3016.73 ± 670.04 ng/mL (p = 0.002) in the DFX-treated group, which was quite significant in contrast to DFP response, where the value was 3204.06 ± 690.15 ng/mL (p = 0.14). There is no statistically significant (p = 0.15) difference on relative changes of the left ventricular ejection fraction (LVEF), between these two groups. The adverse effects were transient and none of them required stoppage of therapy. Deferasirox is more effective when compared to DFP in reducing chelating drug-related complications and iron overload specially in multiple transfusion dependent β-TM patients.

Objectives: Myelodysplastic syndrome (MDS) is a group of myeloid neoplasms. The clinical manifestations and treatments vary depending on the subtype and risk stratification of the disease. There is a paucity of data on Indian patients with MDS. This study was undertaken to understand MDS with regard to their clinical presentation, pathological, cytogenetic profiles and also to assess their therapeutic outcomes and prognosis from our center in Eastern India. Materials and Methods: This is a prospective observational study conducted in the department of hematology at a tertiary care teaching hospital from eastern part of India. The diagnosis of MDS was made from the peripheral blood examination, bone marrow aspirate examination, cytogenetics, and Fluorescence in situ hybridization results, according to the WHO guidelines. Patients were risk stratified using Revised International Prognostic Scoring System (R-IPSS) and subsequent therapeutic planning was done, with either supportive therapy in the form of recombinant human erythropoiesis stimulating agents, colony stimulating factors, packed red blood cell support as needed for low risk MDS patients. High risk patients were treated with hypomethylating agents such as Azacytidine, Decitabine, or Lenalidomide. Results: The mean duration of follow-up of patients with MDS from the point of diagnosis was 1.8 years (range 4 months–6 years). The median OS was 1.33 years. The median OS in the analysis of our patient cohort with low, intermediate, high, and very high R-IPSS was 1.67 years, 1.33 years, 1.67 years, and 1.67 years, respectively. No patients of very low risk group were identified in our study. Conclusion: Our findings reflect that MDS-MLD with low or intermediate R-IPSS risk groups is the most common types of MDS. Although supportive therapy was used to treat patients irrespective of other therapy given (depending on the risk group of the patient), it was used alone even in higher risk groups due to logistic reasons in some cases. Those patients who received supportive care alone also had a good survival duration. However, a longer follow-up duration is required to firmly establish this outcome. The median age of patients (55 years) was also lower than established studies with a median overall survival of 1.67 years.

Objectives: To describe the case series of patients with myeloid sarcoma with their clinicopathological characteristics, cytogenetics, molecular markers, prognosis, and outcome. Material and Methods: Retrospective retrieval of data of myeloid sarcoma cases in acute myeloid leukemia was done from the electronic health records of our hospital and this case series includes the data of three years starting from January 2018 and the follow-up information was assimilated until December 2020. Results: We present twelve patients in this case series with myeloid sarcoma and all these patients had bone marrow involvement at presentation. Most of the cases were less than 20 years of age and orbit (66.7%) was the commonest site of presentation in this series. Aberrant CD 19 expression on immunophenotyping was a common associate (66.9%) and t(8;21) was the commonest cytogenetic abnormality reported in our case series. Despite of high dose intensive therapy with daunorubicin and cytarabine followed by high-dose cytarabine (HiDAC) consolidation, patients had a median relapse-free survival and median overall survival of 160 days and 299.5 days respectively. Local radiotherapy for consolidation in two of our patients had no additional benefit. Conclusion: Myeloid sarcoma is extramedullary collection of myeloid blasts with or without bone marrow involvement. They were commonly seen in young patients and t(8;21) being a common cytogenetic abnormality associated with it. The treatment outcome of patients with myeloid sarcoma seems dismal and systemic therapy remains the modality of choice.

Introduction Acute leukemia (AL) is among the most common treatable cancers in childhood but many children are forced to abandon therapy. Objective We have explored reasons for treatment abandonment through this study. Materials and Methods Retrospective analysis from an ongoing registry data of childhood AL patients, where all newly diagnosed AL patients of ≤18 years of age (June 2014–November 2017) were included. Patients >18 years of age, having any history of treatment of AL outside our institute, and/or patients with relapsed AL were excluded. The primary outcome of the study was treatment abandonment rate. Results A total of 710 AL patients were included in the study, average distance traversed to reach the hospital being 161.66 km. Most children were aged 1 to 10 years (49.4%, n = 351), followed by >10 to 18 years (46.6%, n = 331), and ≤1 year age (3.9%, n = 28). The commonest symptoms were fever (67.4%), pallor (38.6%), bleeding (11.5%), bone pain (13.8%), neck swellings (14.9%), and, rarely, testicular swellings or Superior vena cava (SVC) syndrome (1.1%). A high abandonment rate was noted prior to leukemia subtyping (35.2%, n = 250) mostly among males 62% (n = 155) and the 1- to 10-year group 55.6% (n = 139). A total of 460 (64.8%) patients were subsequently subcategorized by immunophenotyping. Precursor B-cell (Pre-B) Acute Lymphoblastic Leukemia (ALL) in 307 (43.2%) patients was the commonest subtype, followed by early Pre-B ALL (Pro-B ALL) in 10 (1.4%), T-cell ALL (T-ALL) in 51 (7.1%), Acute Myeloid Leukemia (AML) in 45 (6.3%), Acute Promyelocytic Leukemia (APML) in 28 (3.9%), and Mixed Phenotypic Acute Leukemia (MPAL) in 19 (2.6%). Conclusion The most common group of patients was aged 1 to 10 years (median age: 5 years). An abandonment rate of 35.2% was seen prior to complete diagnostic workup. The reason for this high abandonment, despite good disease prognosis, is a relevant social and health issue, and needs further evaluation. The problems discussed in this study are relevant to lower-income families and areas where health care is not easily accessible. The government agencies, nongovernment organizations and society would need to work together to overcome these issues.

Imatinib, the first Tyrosine Kinase Inhibitor (TKI) used for the treatment of chronic myeloid leukaemia (CML) has revolutionized the management by inhibiting BCR-ABL tyrosine kinase. According to earlier reports there are concerns regarding the adverse effect of imatinib on haemostasis by causing platelet dysfunction. Here we studied platelet function using platelet aggregometry, in 19 CML chronic phase (CML-CP) patients on imatinib therapy, in complete haematologic response (CHR). The median duration of imatinib therapy before performing the test was 154 days. This study reveals that there are large inter-individual variations in platelet functions among imatinib treated patients and different levels of variability have been seen for different agonists. Most common aggregation abnormality (

Survivors of acute lymphoblastic leukemia (ALL), though cured of their primary disease may suffer from long-term complications such as bone infarction contributing to a major morbidity. Here, we report a very rare case of bone infarct in bilateral tibia and femur of a patient of acute lymphoblastic leukemia, post completion of maintenance chemotherapy. With this case report, we suggest that appropriate preventive measures are necessary to decrease the risk of this very rare morbidity.

To investigate the effectiveness of low dose secondary/tertiary prophylaxis in severe Hemophilia A children and determine improvements in their daily life. Thirty Hemophilia A children (≤ 12 y) with factor VIII

Although aplastic anemia has been extensively investigated, little is known about their circulating cytokine pattern. The present study was done to evaluate the severity of the disease with the 3 major anti-hematopoietic cytokines interleukin-2 (IL-2), tumor necrosis factor-alpha (TNF-α), and interferon-gamma (IFN-γ). This study is ethically cleared. A total of 102 bone marrow plasma and peripheral blood plasma paired samples were collected from the confirmed acquired aplastic anemia (AAA) patients and 10 control cases after taking written consent and analyzed by the quantitative enzyme-linked immunosorbent assay. The Mann-Whitney U test was used for statistical analysis. Considerably increased levels of IL-2, TNF-α, and IFN-γ were found in the peripheral blood plasma and bone marrow plasma of AAA patients as compared with controls, that is, 45.76±20.61 versus 1.99±1.25, P

Patients with immune thrombocytopenia (ITP) exhibit striking heterogeneity in bleeding manifestations even at similar platelet counts. We report the prevalence and impact of thrombophilia marker expression in chronic ITP patients. For the present study, patients with chronic ITP were clinically assessed at regular intervals using the bleeding assessment tool for ITP, and bleeding was compared among patients with and without thrombophilia marker expression (thrombophilia markers analyzed included clot-based assays for protein C, protein S, Pro C Global®, FVIII levels, and lupus anticoagulant assay). Thirty-six patients (25.5%) tested positive for at least one thrombophilia marker, and the remaining 105 patients (74.5%) were negative for all markers. Patients expressing at least one thrombophilia marker had significantly less bleeding than those without. We conclude that a part of heterogeneity in the clinical presentation of chronic ITP can be explained by the presence of thrombophilia.

Beta-hemoglobinopathies exhibit a heterogeneous clinical picture with varying degrees of clinical severity. Pertaining to the limited treatment options available, where blood transfusion still remains the commonest mode of treatment, pharmacological induction of fetal hemoglobin (HbF) has been a lucrative therapeutic intervention. Till now more than 70 different HbF inducers have been identified. The practical usage of many pharmacological drugs has been limited due to safety concerns. Natural compounds, like Resveratrol, Ripamycin and Bergaptene, with limited cytotoxicity and high efficacy have started capturing the attention of researchers. In this review, we have summarized pharmacological drugs and bioactive compounds isolated from natural sources that have been shown to increase HbF significantly. It primarily discusses recently identified synthetic and natural compounds, their mechanism of action, and their suitable screening platforms, including high throughput drug screening technology and biosensors. It also delves into the topic of combinatorial therapy and drug repurposing for HbF induction. Overall, we aim to provide insights into where we stand in HbF induction strategies for treating β-hemoglobinopathies.

Introduction Selinexor is a first-in-class, oral, potent selective inhibitor of nuclear export (SINE) which blocks XPO1, forcing the nuclear retention and activation of tumor suppressor proteins, leading to cancer cell apoptosis. Selinexor has demonstrated antimyeloma activity in triple class refractory multiple myeloma (MM) [Chari et al. NEJM 2019]. Selinexor synergizes with proteasome inhibitors (PIs) in PI-sensitive and -resistant cell lines and produces high response rates in patients with PI refractory and non-refractory MM (Bahlis et al. Blood 2018). In the phase 3 BOSTON study, the combination of once weekly (QW) selinexor, QW bortezomib, and dexamethasone (SVd) in patients who had received 1-3 prior therapies led to a significantly longer (47%) median progression-free survival (PFS) of 13.93 vs 9.46 months, with a hazard ratio of 0.70 (P=0.0075) compared to standard twice weekly bortezomib and dexamethasone (Vd). In addition, SVd regimen produced higher response rates and deeper responses (ORR: 76.4% vs 62.3% and ≥CR 16.9% vs 10.2%) compared with Vd. The benefit with SVd was observed across all efficacy endpoints and was associated with lower incidence and severity of bortezomib-induced peripheral neuropathy. Here we analyzed the effect of prior PI therapy (bortezomib, carfilzomib, ixazomib) on the efficacy and safety of SVd compared with Vd. Methods BOSTON is an open-label, randomized phase 3 study in patients with MM comparing SVd (QW oral selinexor 100 mg, QW subcutaneous bortezomib 1.3 mg/m2, and BIW oral dexamethasone 20 mg), versus Vd (BIW bortezomib 1.3 mg/m2 and QIW dexamethasone 20 mg). Patients previously treated with a PI must have had at least a partial response (PR) to the PI and 6 months since the last PI regimen. The study primary end point was PFS. Here we report subgroup analysis of treatment outcomes based on prior PI treatment. Results Subgroups consisted of PI naïve patients (n=95; 24%) and patients with prior PI treatment (n=307; 76%). Both the subgroups and study arms were comparable for baseline patient demographic and disease characteristics. However, those with prior PI treatment more frequently had a previous stem cell transplant (38% vs 24%) or 3 lines of prior anti MM therapy (21% vs 13%). Median PFS was improved with SVd compared with Vd in both the PI naïve group (PFS not reached (NR) vs 9.7 months; HR 0.2585 [95% CI, 0.1116-0.5988]; P=0.0003) and in the PI treated group (11.7 vs 9.4 months; HR 0.7839 [95% CI, 0.5791-1.0612]; P=0.06). Other efficacy endpoints are shown in the table. Peripheral neuropathy ≥grade 2 (a secondary study endpoint) was less frequent in the SVd compared with the Vd arm (PI naïve: 25.5%, Vd 43.8%, P=0.0302; PI treated: SVd 19.6%, Vd 31.4%, P=0.0092). Adverse events of ≥grade 3 occurred in 71% of patients in the PI naïve group (SVd 77%, Vd 65%) and 74% of patients in the PI treated group (SVd 88%, Vd 60%). Thrombocytopenia was more frequent in patients in the SVd arms (PI naïve: SVd 32%, Vd 13%; PI treated: SVd 42%, Vd 19%) as was anemia (PI naïve: SVd 15%, Vd 6%; PI treated: SVd 16%, Vd 12%), and fatigue (PI naïve: SVd 15%, Vd 2%; PI treated: SVd 13%, Vd 1%). Conclusions The once-weekly SVd combination was associated with significant clinical benefit and reduced peripheral neuropathy as compared with standard twice-weekly Vd in patients with MM and 1-3 prior therapies, regardless of prior therapy with a PI. However, the benefits of SVd over Vd were more pronounced in patients who had never been treated with a PI (PFS HR 0.26), suggesting that selinexor could be an optimal partner for combining with weekly bortezomib as the first PI-containing MM regimen. Figure 1 Disclosures Mateos: Roche: Honoraria; Seattle Genetics: Honoraria; EDO Mundipharma: Honoraria; Adaptive Biotechnologies: Honoraria; GlaxoSmithKline: Honoraria; Abbvie: Honoraria; Takeda: Honoraria; Amgen: Honoraria; Bristol-Myers Squibb: Honoraria; Janssen: Honoraria. Gavriatopoulou:Amgen: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Genesis Pharma: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria. Facon:Celgene, Janssen, Takeda, Amgen, Roche, Karyopharm, Oncopeptides, BMS, Sanofi: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Auner:Karyopharm: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Research Funding. Leleu:AbbVie: Honoraria; GSK: Honoraria; Amgen: Honoraria; Novartis: Honoraria; Carsgen: Honoraria; Incyte: Honoraria; Merck: Honoraria; BMS-celgene: Honoraria; Janssen: Honoraria; Oncopeptide: Honoraria; Sanofi: Honoraria; Karyopharm: Honoraria. Hajek:Novartis: Consultancy, Honoraria, Research Funding; Roche: Consultancy, Honoraria, Research Funding; Oncopeptides: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharma MAR: Consultancy, Honoraria; BMS: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Dimopoulos:Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, Research Funding, Speakers Bureau; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, Speakers Bureau; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, Research Funding, Speakers Bureau. Delimpasi:GENESIS: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Amgen: Consultancy, Honoraria. Spicka:Celgene, Amgen, Janssen-Cilag, Takeda, Bristol-Myers Squibb, Novartis, Sanofi: Consultancy, Honoraria, Speakers Bureau. Kryachok:Janssen, Bayer, Karyopharm, MSD, Acerta, AvbbVie, Debiopharm: Research Funding; Takeda, Janssen: Consultancy; Takeda, MSD, AbbVie, Ro: Other: Travel, accommodations, expenses; Takeda, Janssen, Novartis, Roche, MSD, Bayer: Consultancy, Research Funding. Sinha:Dr Reddys Lab, Intas Pharmaceuticals, Karyopharm Therapeutics: Honoraria. Venner:Celgene, Amgen: Research Funding; Janssen, BMS/Celgene, Sanofi, Takeda, Amgen: Honoraria. Garg:Janssen, Takeda, Celgene, Novartis, Sanofi: Honoraria. Stevens:Amgen, MorphoSys: Consultancy. Quach:GlaxoSmithKline: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy, Research Funding; Glaxo Kline Smith: Consultancy, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Janssen Cilag: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria, Research Funding. Jagannath:BMS, Janssen, Karyopharm, Legend Biotech, Sanofi, Takeda: Consultancy. Moreau:Amgen: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Takeda: Honoraria; Janssen: Consultancy, Honoraria; Celgene/Bristol-Myers Squibb: Consultancy, Honoraria; Novartis: Honoraria. Levy:Karyopharm,Takeda, BMS: Consultancy, Honoraria, Speakers Bureau. Badros:Amgen: Consultancy; University of Maryland: Current Employment. Anderson:Karyopharm: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; GSK: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding. Bahlis:Sanofi: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; BMS/Celgene and Janssen: Consultancy, Honoraria, Other: Travel, Accomodations, Research Funding; AbbVie: Consultancy, Honoraria; Genentech: Consultancy, Honoraria; Karyopharm Therapeutics: Consultancy, Honoraria; GSK: Consultancy, Honoraria. Cavo:Jannsen, BMS, Celgene, Sanofi, GlaxoSmithKline, Takeda, Amgen, Oncopeptides, AbbVie, Karyopharm, Adaptive: Consultancy, Honoraria. Chai:Karyopharm Therapeutics Inc: Current Employment. Arazy:Karyopharm Therapeutics Inc.: Current Employment. Shah:Karyopharm Therapeutics Inc: Current Employment, Current equity holder in publicly-traded company. Shacham:Karyopharm: Current Employment, Current equity holder in publicly-traded company, Patents & Royalties: (8999996, 9079865, 9714226, PCT/US12/048319, and I574957) on hydrazide containing nuclear transport modulators and uses, and pending patents PCT/US12/048319, 499/2012, PI20102724, and 2012000928) . Kauffman:Karyopharm Therapeutics Inc: Current Employment, Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees. Richardson:Celgene/BMS, Oncopeptides, Takeda, Karyopharm: Research Funding.

Introduction Selinexor is a first-in-class, oral, potent selective inhibitor of nuclear export (SINE) which blocks XPO1, forcing the nuclear retention and activation of tumor suppressor proteins, leading to cancer cell apoptosis. Selinexor has demonstrated antimyeloma activity in triple class refractory multiple myeloma (MM) [Chari et al. NEJM 2019]. Selinexor synergizes with proteasome inhibitors (PIs) in PI-sensitive and -resistant cell lines and produces high response rates in patients with PI refractory and non-refractory MM. (Bahlis et al. Blood 2018). In the phase 3 BOSTON study, the combination of once weekly (QW) selinexor, QW bortezomib and dexamethasone (SVd) in patients who had received 1-3 prior therapies led to a significantly (47%) longer median progression-free survival (PFS) of 13.93 versus 9.46 months (HR 0.70; P=0.0075) compared to standard twice weekly bortezomib and dexamethasone (Vd). In addition, SVd regimen produced higher response rates and deeper responses (ORR: 76.4% vs 62.3% and ≥CR 16.9% vs 10.2%) compared with Vd. The benefit with SVd was observed across all efficacy endpoints and was associated with lower incidence and severity of bortezomib-induced peripheral neuropathy. Here we present subgroup analyses according to number of prior lines of therapy and prior treatment with lenalidomide (LEN). Methods BOSTON is an open-label, randomized phase 3 study in patients with MM comparing SVd (QW selinexor 100 mg, QW subcutaneous bortezomib 1.3 mg/m2, and 20 mg twice weekly [BIW] dexamethasone), versus Vd (1.3 mg/m2 bortezomib BIW and dexamethasone 20 mg 4 x weekly [QIW]). Patients previously treated with a PI must have had at least a partial response (PR) to the PI and 6 months since the last PI regimen. The study primary end point was PFS. Results Of the 402 patients in the BOSTON study, 198 (49%) had 1 prior line versus 204 (51%) with 2-3 prior lines. In addition, 154 (38%) comprised the LEN treated subgroup, versus 248 (62%) in the LEN naïve subgroup. Of note, 41% patients received prior thalidomide, which is consistent with most of the BOSTON study patients being treated in the EU. Baseline demographic and disease characteristics were well balanced between treatment arms across subgroups. A very good partial response (VGPR) or better to most recent prior line anti-MM therapy was more frequent in patients with 1 prior line of therapy (63% vs 41%) versus those with 2-3 prior lines of therapy. Patients with prior LEN therapy were more likely to have had 2-3 prior therapies (72.1%) compared with LEN naive patients (37.5%). As shown in the table, SVd was associated with longer PFS compared with Vd in all subgroups. Overall response rates (ORR) and times-to-next-treatment (TTNT) were statistically greater with SVd compared with Vd in all subgroups. Rates of very good partial response or better (VGPR) were statistically greater for SVd vs Vd in the LEN-naïve group and 1 prior treatment group. Grade ≥2 peripheral neuropathy (a key secondary endpoint prespecified in the study) occurred less frequently across all SVd subgroups compared with Vd: LEN treated (21% SVd, 37% Vd, P=0.0166); LEN-naïve (21% SVd, 33% Vd, P=0.0252), 1 prior line (21% SVd, 33% Vd, P=0.0501); 2-3 prior lines (21% SVd, 36% Vd, P=0.0107). Adverse events of ≥grade 3 were more commonly reported in the SVd treatment arm than in the Vd arm, LEN treated (83% SVd, 57% Vd), LEN-naïve (76% SVd, 55% Vd), 1 prior line (77% SVd, 56% Vd), 2-3 prior lines (81% SVd, 56% Vd), and were mostly managed with dose modification and/or supportive treatment. Pneumonia occurred at comparable rates between treatment arms. There were no differences between subgroups in grade 3 adverse events. Conclusions In the BOSTON study, once-weekly SVd significantly improved PFS, ORR, TTNT and reduced rates of ≥grade 2 peripheral neuropathy compared with Vd regardless of number of prior treatments or whether patients were previously treated with LEN. Adverse events were managed with dose modification and treatment-related discontinuation rates did not differ between the 2 regimens for any subgroup. The PFS of 16.6 months with SVd after 1 prior therapy, and the HR of 0.63 in patients with prior LEN treatment support the use of once-weekly SVd for the second line treatment of MM following a LEN-containing regimen. Table Disclosures Mateos: Takeda: Honoraria; Abbvie: Honoraria; GlaxoSmithKline: Honoraria; EDO Mundipharma: Honoraria; Seattle Genetics: Honoraria; Roche: Honoraria; Bristol-Myers Squibb: Honoraria; Janssen: Honoraria; Amgen: Honoraria; Adaptive Biotechnologies: Honoraria. Jagannath:Takeda: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Legend Biotech: Consultancy, Honoraria. Delimpasi:GENESIS: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Amgen: Consultancy, Honoraria. Spicka:Celgene, Amgen, Janssen-Cilag, Takeda, Bristol-Myers Squibb, Novartis, Sanofi: Consultancy, Honoraria, Speakers Bureau. Kryachok:Takeda, Janssen, Novartis, Roche, MSD, Bayer: Consultancy, Research Funding; Janssen, Bayer, Karyopharm, MSD, Acerta, AvbbVie, Debiopharm: Research Funding; Takeda, MSD, AbbVie, Ro: Other: Travel, accommodations, expenses; Takeda, Janssen: Consultancy. Gavriatopoulou:Amgen: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Genesis Pharma: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria. Dimopoulos:Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, Speakers Bureau; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, Research Funding, Speakers Bureau; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees. Auner:Amgen: Consultancy, Honoraria, Research Funding; Karyopharm: Consultancy, Honoraria; Takeda: Consultancy, Honoraria. Leleu:BMS-celgene: Honoraria; Carsgen: Honoraria; Incyte: Honoraria; Merck: Honoraria; AbbVie: Honoraria; Oncopeptide: Honoraria; Janssen: Honoraria; Novartis: Honoraria; Amgen: Honoraria; GSK: Honoraria; Sanofi: Honoraria; Karyopharm: Honoraria. Sinha:Dr Reddys Lab, Intas Pharmaceuticals, Karyopharm Therapeutics: Honoraria. Venner:Celgene, Amgen: Research Funding; Janssen, BMS/Celgene, Sanofi, Takeda, Amgen: Honoraria. Garg:Janssen, Takeda, Celgene, Novartis, Sanofi: Honoraria. Stevens:Amgen, MorphoSys: Consultancy. Quach:Amgen, Celgene, karyopharm, GSK, Janssen Cilag, Sanofi.: Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline, Karyopharm, Amgen, Celgene, Janssen Cilag: Honoraria; GlaxoSmithKline, Karyopharm, Amgen, Celgene, Janssen Cilag: Consultancy; Amgen, sanofi, celgene, Karyopharm, GSK: Research Funding. Moreau:Novartis: Honoraria; Amgen: Consultancy, Honoraria; Celgene/Bristol-Myers Squibb: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Takeda: Honoraria; Sanofi: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria. Levy:Sanofi: Consultancy, Honoraria, Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; Karyopharm: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Bristol Meyers Squibb: Consultancy, Honoraria, Research Funding; AstraZeneca: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding; BeiGene: Consultancy, Research Funding, Speakers Bureau; Baylor University Med Center: Current Employment; Takeda: Consultancy, Honoraria, Research Funding. Badros:Amgen: Consultancy; University of Maryland: Current Employment. Anderson:Janssen: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; GSK: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria, Research Funding; Karyopharm: Consultancy, Honoraria, Research Funding. Bahlis:Genentech: Consultancy, Honoraria; Karyopharm Therapeutics: Consultancy, Honoraria; GSK: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria; BMS/Celgene and Janssen: Consultancy, Honoraria, Other: Travel, Accomodations, Research Funding; Sanofi: Consultancy, Honoraria. Facon:Celgene, Janssen, Takeda, Amgen, Roche, Karyopharm, Oncopeptides, BMS, Sanofi: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Cavo:Jannsen, BMS, Celgene, Sanofi, GlaxoSmithKline, Takeda, Amgen, Oncopeptides, AbbVie, Karyopharm, Adaptive: Consultancy, Honoraria. Chai:Karyopharm Therapeutics Inc: Current Employment. Arazy:Karyopharm Therapeutics Inc.: Current Employment. Shah:Karyopharm Therapeutics Inc: Current Employment, Current equity holder in publicly-traded company. Shacham:Karyopharm: Current Employment, Current equity holder in publicly-traded company, Patents & Royalties: (8999996, 9079865, 9714226, PCT/US12/048319, and I574957) on hydrazide containing nuclear transport modulators and uses, and pending patents PCT/US12/048319, 499/2012, PI20102724, and 2012000928) . Kauffman:Karyopharm Therapeutics Inc: Current Employment, Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees. Richardson:Celgene/BMS, Oncopeptides, Takeda, Karyopharm: Research Funding.

The current study was conducted to assess response to immunosuppressive therapy (IST) in acquired aplastic anaemia (AA). It was a retrospective and prospective observational study. Patients were diagnosed as per standard international guidelines and IST was started as per standard protocol. Patients were followed up at 3 months and 6 months for assessment of response as per published standard guidelines. Total 76 cases were included in the study. The median age of the study population was 36 years with a range of 6-66 years with a male to female ratio of 2.04:1. Most common clinical presentation was pallor followed by bleeding. Commonest type of disease in the study group was severe AA. Among total 76 patients, 32 patients received Atgam and 44 patients received Thymogam. Within 3 months of ATG administration, 4 patients died and 1 patient was lost to follow up. At 3 months, 2 (2.63%) patients were on complete response (CR), 32 (42.10%) patients were in partial response (PR) and 37 (48.68%) patients were on no response (NR). Overall response (OR) at 3 months was 44.73%. At 6 months 5 (6.57%) patients were in CR, 43 (56.57%) patients in PR and 23 (30.26%) patients in NR; the OR was 63.14%. Overall response at 3 months was 44.73% and overall response at 6 months was 63.14%. The study revealed better overall survival for patients with ATGAM treatment than THYMOGAM treatment arm.

Therapeutic regimens for previously treated multiple myeloma (MM) may not provide prolonged disease control and are often complicated by significant adverse events, including peripheral neuropathy. In patients with previously treated MM in the Phase 3 BOSTON study, once weekly selinexor, once weekly bortezomib, and 40 mg dexamethasone (XVd) demonstrated a significantly longer median progression-free survival (PFS), higher response rates, deeper responses, a trend to improved survival, and reduced incidence and severity of bortezomib-induced peripheral neuropathy when compared with standard twice weekly bortezomib and 80 mg dexamethasone (Vd). The pre-specified analyses described here evaluated the influence of the number of prior lines of therapy, prior treatment with lenalidomide, prior proteasome inhibitor (PI) therapy, prior immunomodulatory drug therapy, and prior autologous stem cell transplant (ASCT) on the efficacy and safety of XVd compared with Vd. In this 1:1 randomized study, enrolled patients were assigned to receive once weekly oral selinexor (100 mg) with once weekly subcutaneous bortezomib (1.3 mg/m2) and 40 mg per week dexamethasone (XVd) versus standard twice weekly bortezomib and 80 mg per week dexamethasone (Vd). XVd significantly improved PFS, overall response rate, time-to-next-treatment, and showed reduced all grade and grade ≥ 2 peripheral neuropathy compared with Vd regardless of prior treatments, but the benefits of XVd over Vd were more pronounced in patients treated earlier in their disease course who had either received only one prior therapy, had never been treated with a PI, or had prior ASCT. Treatment with XVd improved outcomes as compared to Vd regardless of prior therapies as well as manageable and generally reversible adverse events. XVd was associated with clinical benefit and reduced peripheral neuropathy compared to standard Vd in previously treated MM. These results suggest that the once weekly XVd regimen may be optimally administered to patients earlier in their course of disease, as their first bortezomib-containing regimen, and in those relapsing after ASCT.Trial registration: ClinicalTrials.gov (NCT03110562). Registered 12 April 2017. https://clinicaltrials.gov/ct2/show/NCT03110562.

Background There is scarcity of data on outcome of COVID-19 in patients with hematological malignancies. Primary objective of study was to analyse the 14-day and 28-day mortality. Secondary objectives were to correlate age, comorbidities and remission status with outcome. Methods Retrospective multicentre observational study conducted in 11 centres across India. Total 130 patients with hematological malignancies and COVID-19 were enrolled. Results Fever and cough were commonest presentation. Eleven percent patients were incidentally detected. Median age of our cohort was 49.5 years. Most of our patients had a lymphoid malignancy (n = 91). One-half patients (52%) had mild infection, while moderate and severe infections contributed to one-fourth each. Sixty seven patients (52%) needed oxygen For treatment of COVID-19 infection, half(n = 66) received antivirals. Median time to RT-PCR COVID-19 negativity was 17 days (7–49 days). Nearly three-fourth (n = 95) of our patients were on anticancer treatment at time of infection, of which nearly two-third (n = 59;64%) had a delay in chemotherapy. Overall, 20% (n = 26) patients succumbed. 14-day survival and 28-day survival for whole cohort was 85.4% and 80%, respectively. One patient succumbed outside the study period on day 39. Importantly, death rate at 1 month was 50% and 60% in relapse/refractory and severe disease cohorts, respectively. Elderly patients(age ≥ 60) (p = 0.009), and severe COVID-19 infection (p = 0.000) had a poor 14-day survival. The 28-day survival was significantly better for patients in remission (p = 0.04), non-severe infection (p = 0.00), and age Conclusions Elderly patients with hematological malignancy and severe covid-19 have worst outcomes specially when disease is not in remission.

The SARS-CoV-2 (COVID-19) pandemic is a worldwide public health emergency with widespread impact on health care delivery. Unforeseen challenges have been noted during administration of usual haematology care in these unusual COVID-19 times. Medical services have been overstretched and frontline health workers have borne the brunt of COVID-19 pandemic. Movement restrictions during lockdown prevented large sections of population from accessing health care, blood banks from holding blood drives, and disrupted delivery of diagnostic hematology services. The disruption in hematology care due to COVID-19 pandemic in India has been disproportionately higher compared to other subspecialities as hematology practice in India remains restricted to major cities. In this review we chronicle the challenges encountered in caring for hematology patients during the COVID-19 pandemic in India and put forth recommendations for minimizing their impact on provision of hematology care with special emphasis on hematology practice in lower and middle income countries (LMICs).

Elderly and frail patients with multiple myeloma (MM) are more vulnerable to the toxicity of combination therapies, often resulting in treatment modifications and suboptimal outcomes. The phase 3 BOSTON study showed that once-weekly selinexor and bortezomib with low-dose dexamethasone (XVd) improved PFS and ORR compared with standard twice-weekly bortezomib and moderate-dose dexamethasone (Vd) in patients with previously treated MM. This is a retrospective subgroup analysis of the multicenter, prospective, randomized BOSTON trial. Post hoc analyses were performed to compare XVd versus Vd safety and efficacy according to age and frailty status (

In the phase 3 BOSTON study, patients with multiple myeloma (MM) after 1–3 prior regimens were randomized to once-weekly selinexor (an oral inhibitor of exportin 1 [XPO1]) plus bortezomib-dexamethasone (XVd) or twice-weekly bortezomib-dexamethasone (Vd). Compared with Vd, XVd was associated with significant improvements in median progression-free survival (PFS), overall response rate (ORR), and lower rates of peripheral neuropathy, with trends in overall survival (OS) favoring XVd. In BOSTON, 141 (35.1%) patients had MM with high-risk (presence of del[17p], t[4;14], t[14;16], or ≥4 copies of amp1q21) cytogenetics (XVd, n=70; Vd, n=71), and 261 (64.9%) exhibited standard-risk cytogenetics (XVd, n=125; Vd, n=136). Among patients with high-risk MM, median PFS was 12.91 months for XVd and 8.61 months for Vd (HR, 0.73 [95% CI, (0.4673, 1.1406)], p=0.082), and ORRs were 78.6% and 57.7%, respectively (OR 2.68; p= 0.004). In the standard-risk subgroup, median PFS was 16.62 months for XVd and 9.46 months for Vd (HR 0.61; p=0.004), and ORRs were 75.2% and 64.7%, respectively (OR 1.65; p=0.033). The safety profiles of XVd and Vd in both subgroups were consistent with the overall population. These data suggest that selinexor can confer benefits to patients with MM regardless of cytogenetic risk. ClinicalTrials.gov identifier: NCT03110562.

Thalassemia and hemoglobinopathies are the most common cause of high morbidity and mortality in India. Detection of carriers and premarital counseling play an important role in preventing the birth of a thalassemic child. The present study aimed to detect large numbers of asymptomatic carriers in rural areas of West Bengal, India. The present cross-sectional study was conducted over a period of 10 years. Thalassemia awareness programs and detection camps were organized at the community level. After signed written consent was obtained, the collected blood samples were subjected to a complete blood count (CBC) in an automated blood cell counter and then analyzed by high performance liquid chromatography (HPLC); in difficult cases, samples were sent to the reference laboratory for molecular characterization. Out of 287,258 samples collected, 32,921 (11.46%) cases revealed abnormal hemoglobins (Hbs); of these, 31,782 (11.06%) carried heterozygous states (carriers/traits), and the remainder were either homozygous or compound heterozygous for different hemoglobinopathies. Two common variants were revealed in the study, namely β-thalassemia (β-thal) (7.23%) and Hb E [β26(B8)Glu→Lys

In India, CML is the commonest adult leukemia. Imatinib is the gold standard for frontline treatment of newly diagnosed CML-CP patients. The present study was conducted to assess the efficacy and safety of generic imatinib in newly diagnosed CML-CP patients. In this prospective study, 76 newly diagnosed CML-CP patients received generic imatinib. They were monitored as per the ELN2013 recommendation. Karyotyping and BCR-ABL transcript level were done at specified time points. Adverse effects, if any, were documented as per the NCI-CTCAE criteria v4.03. Statistical analysis was done using standard methods. A total of 76 patients included in the study; median age was 36 years. The most common (71%) presenting symptom was fatigue; splenomegaly was found in all patients. CHR was achieved in 97% cases. At 3 months, 64.5% patients achieved ERM. At 6 months, CCyR and MCyR had seen in 65% and 68% cases, respectively. MMR achieved at 12 months in 44% cases. Most common hematological and non-hematological toxicity were anemia and skin changes seen in 89.5% and 71% cases, respectively. With generic imatinib therapy, the results of treatment outcome and safety profile were comparable with original imatinib. The added advantage was gross reduction in cost of therapy meeting unmet needs in CML patients in countries with resource constraints.

Summary Background Selinexor combined with dexamethasone has shown activity in patients with heavily pre-treated multiple myeloma. In a phase 1b/2 study, the combination of oral selinexor with bortezomib (a proteasome inhibitor) and dexamethasone induced high response rates with low rates of peripheral neuropathy, the main dose-limiting toxicity of bortezomib. We aimed to evaluate the clinical benefit of weekly selinexor, bortezomib, and dexamethasone versus standard bortezomib and dexamethasone in patients with previously treated multiple myeloma. Methods This phase 3, randomised, open-label trial was done at 123 sites in 21 countries. Patients aged 18 years or older, who had multiple myeloma, and who had previously been treated with one to three lines of therapy, including proteasome inhibitors, were randomly allocated (1:1) to receive selinexor (100 mg once per week), bortezomib (1·3 mg/m2 once per week), and dexamethasone (20 mg twice per week), or bortezomib (1·3 mg/m2 twice per week for the first 24 weeks and once per week thereafter) and dexamethasone (20 mg four times per week for the first 24 weeks and twice per week thereafter). Randomisation was done using interactive response technology and stratified by previous proteasome inhibitor therapy, lines of treatment, and multiple myeloma stage. The primary endpoint was progression-free survival in the intention-to-treat population. Patients who received at least one dose of study treatment were included in the safety population. This trial is registered at ClinicalTrials.gov , NCT03110562 . The trial is ongoing, with 55 patients remaining on randomised therapy as of Feb 20, 2020. Findings Of 457 patients screened for eligibility, 402 were randomly allocated—195 (49%) to the selinexor, bortezomib, and dexamethasone group and 207 (51%) to the bortezomib and dexamethasone group—and the first dose of study medication was given between June 6, 2017, and Feb 5, 2019. Median follow-up durations were 13·2 months [IQR 6·2–19·8] for the selinexor, bortezomib, and dexamethasone group and 16·5 months [9·4–19·8] for the bortezomib and dexamethasone group. Median progression-free survival was 13·93 months (95% CI 11·73–not evaluable) with selinexor, bortezomib, and dexamethasone and 9·46 months (8·11–10·78) with bortezomib and dexamethasone (hazard ratio 0·70 [95% CI 0·53–0·93], p=0·0075). The most frequent grade 3–4 adverse events were thrombocytopenia (77 [39%] of 195 patients in the selinexor, bortezomib, and dexamethasone group vs 35 [17%] of 204 in the bortezomib and dexamethasone group), fatigue (26 [13%] vs two [1%]), anaemia (31 [16%] vs 20 [10%]), and pneumonia (22 [11%] vs 22 [11%]). Peripheral neuropathy of grade 2 or above was less frequent with selinexor, bortezomib, and dexamethasone (41 [21%] patients) than with bortezomib and dexamethasone (70 [34%] patients; odds ratio 0·50 [95% CI 0·32–0·79], p=0·0013). 47 (24%) patients in the selinexor, bortezomib, and dexamethasone group and 62 (30%) in the bortezomib and dexamethasone group died. Interpretation A once-per-week regimen of selinexor, bortezomib, and dexamethasone is a novel, effective, and convenient treatment option for patients with multiple myeloma who have received one to three previous lines of therapy. Funding Karyopharm Therapeutics.

Azacitidine is one of the hypomethylating agents used for management of myelodysplastic syndrome (MDS). A 68-year-old male was diagnosed as a case of MDS Excess Blast-2 and was started with subcutaneous azacitidine injection. After two days, he developed erythematous maculopapular lesions of varying sizes over the trunk and extremities associated with itching. While toxic reaction at the injection site is common, allergic reaction is not widely known. It requires attention to systemic skin reactions because the incidences are likely to increase with the increasing use of Azacitidine.

Hb E-beta thalassemia is a major public health problem in West Bengal, India and is the predominant symptom producing thalassemia in this part of the country. To search for an easy, reliable and cost effective screening method for HbE that can be used at the community level where more sophisticated methods are not readily available. And the DCIP test was performed for the purpose. Blood samples of 425 asymptomatic family members from 80 diagnosed cases of HbE beta Thalassemia patients were tested for Hb, RBC indices, DCIP test, HPLC, and in discordant cases confirmed by DNA mutation analysis. The present study shows DCIP screening test to have a sensitivity, specificity, positive predictive value and negative predictive value of 96.39%, 97.43%, 96.39% and 97.43% respectively. It also shows a false positive rate and false negative rate in 2.56% and 4.6% cases respectively. The advantage with DCIP over HPLC is that it can be easily performed at the community level by a person with minimum technical skill, few samples (even a single sample) can be tested at time, at a low cost.

Introduction: Treatment of multiple myeloma (MM) has greatly improved over the last two decades. However, most pts will relapse and develop refractory disease. Most anti-cancer regimens require dose modifications (interruption, reduction, or discontinuation) during the treatment course in order to optimize the therapeutic window; appropriate modifications improve tolerability while maintaining anti-cancer activity. Selinexor, an oral selective inhibitor of XPO1-mediated nuclear export (SINE) compound, enforces the nuclear retention and functional activation of tumor suppressor proteins within the nucleus and prevents the translation of oncoproteins. The combination of once weekly (QW) selinexor, QW bortezomib, and dexamethasone (XVd) is FDA approved for previously treated MM. Compared to standard twice weekly (BIW) bortezomib plus dexamethasone (Vd) and using 40% less bortezomib and 25% less dexamethasone, XVd demonstrated significantly prolonged median progression-free survival (PFS) and time-to-next-treatment (TTNT), increased the overall response rate (ORR), reduced rates of peripheral neuropathy, and showed a trend towards improved overall survival (OS) in the Phase 3 randomized BOSTON study (NCT03110562). The recommended starting dose of selinexor in XVd is 100mg QW, but the median dose administered in BOSTON was 80 mg QW. Here, we analyzed the efficacy outcomes and adverse events (AEs) in pts whose dose was reduced compared to those where it was not. Methods: The BOSTON study consisted of two arms: pts treated with selinexor QW (100mg), bortezomib QW (1.3mg/m 2) and dexamethasone BIW (20 mg) (XVd; n=195 in the intention-to-treat [ITT] population) compared to standard BIW Vd. Results: Of the XVd pts in the BOSTON study, 126 had a dose reduction of selinexor and 69 did not. The median age was 66.0 in both groups (range: with reduction, 47-87; without, 40-84) and the median number of prior therapies was 1.0 (range, 1-3) for both groups (Table 1). The median time to dose reduction in these pts was 68 days (range, 8-561 days). The median duration of study treatment for these pts was 34.5 weeks (range, 3-120 weeks) compared to 20.0 weeks (range, 1-118) in pts with no dose reduction. In the group with dose reduction, the median dose of selinexor received per week was 71.3 mg (range, 29.7, 101.4) compared to 100 mg (range, 33.3, 136.7) in pts with no reduction. Pts who dose reduced had a median PFS of 16.6 months compared to 9.2 months in pts who did not (one-sided p value, The most common adverse events (AEs; dose reduction and without dose reduction) of any grade were thrombocytopenia (69.8% and 42.0%), nausea (55.6% and 40.6%), and fatigue (49.2% and 29.0%). The rate of treatment discontinuation in the dose reduced group was 24.6% and 14.5% without dose reductions. In the dose reduced group, there were 6 (4.8%) deaths and 6 (8.7%) in the group with no dose reduction. As pts with a dose reduction stayed on therapy for a prolonged period of time, to best understand the impact of dose reduction on the AE, we present the duration-adjusted incidence rates of AEs of clinical interest. The duration-adjusted incidence rates of AE were considerably lower after dose reduction of selinexor compared to the rates on or before dose reduction: thrombocytopenia (62.5% vs 47.6%), nausea (31.6% vs 7.3%), fatigue (28.1% vs 9.9%), decreased appetite (21.5% vs 6.4%), anemia (17.9% vs 10.3%), and diarrhea (12.9% vs 5.2) (Table 3). Conclusions: While all pts on XVd initiated therapy at 100mg selinexor QW, and it was associated with very low rates of progressive disease (1 in 195 pts), appropriate dose reductions of selinexor were associated with a longer PFS, DOR, and TTNT, and significantly reduced AE with improved tolerability, highlighting dose reductions as an important tool to personalize and optimize the therapeutic window for pts with RRMM. Figure 1 Figure 1. Disclosures Jagannath: Bristol Myers Squibb: Consultancy; Janssen Pharmaceuticals: Consultancy; Karyopharm Therapeutics: Consultancy; Legend Biotech: Consultancy; Sanofi: Consultancy; Takeda: Consultancy. Badros: Janssen: Research Funding; GlaxoSmithKline: Research Funding; J&J: Research Funding; BMS: Research Funding. Levy: Takeda, Celgene, Seattle Genetics, AbbVie, Jazz Pharmaceuticals, Gilead Sciences, Bristol-Myers Squibb, Amgen, Spectrum Pharmaceuticals,Janssen.: Consultancy. Moreau: Celgene BMS: Honoraria; Oncopeptides: Honoraria; Amgen: Honoraria; Sanofi: Honoraria; Abbvie: Honoraria; Janssen: Honoraria. Delimpasi: Takeda: Honoraria, Speakers Bureau; Janssen: Honoraria, Speakers Bureau; Amgen: Honoraria, Speakers Bureau. Kriachok: Takeda, Roche, Abbivie, Janssen, MSD: Consultancy; Takeda, Roche, Abbvie, Janssen, MSD, Pfizer: Honoraria, Speakers Bureau. Gavriatopoulou: Takeda: Honoraria; Sanofi: Honoraria; GSK: Honoraria; Janssen: Honoraria; Karyopharm: Honoraria; Genesis: Honoraria; Amgen: Honoraria. Auner: Janssen: Speakers Bureau; Amgen: Research Funding; Takeda, Karyopharm: Other: Advisory role. Leleu: Bristol-Myers Squibb: Honoraria; Carsgen Therapeutics Ltd: Honoraria; Celgene: Honoraria; Gilead Sciences: Honoraria; Janssen-Cilag: Honoraria; Karyopharm Therapeutics: Honoraria; Merck: Honoraria; Mundipharma: Honoraria; Novartis: Honoraria; Oncopeptides: Honoraria; Pierre Fabre: Honoraria; Roche: Honoraria; Sanofi: Honoraria; Amgen: Honoraria; AbbVie: Honoraria; Takeda: Honoraria, Other: Non-financial support. Usenko: Janssen: Consultancy, Honoraria, Other: Clinical Trials Investigator; AbbVie: Consultancy, Honoraria, Other: Clinical Trials Investigator; Pfizer: Consultancy, Honoraria; Acerta: Other: Clinical Trials Investigator; Ascentage: Other: Clinical Trials Investigator; Celgene: Other: Clinical Trials Investigator; Il-Yang: Other: Clinical Trials Investigator; Karyopharm: Other: Clinical Trials Investigator; Oncopeptides: Other: Clinical Trials Investigator; Rigel: Other: Clinical Trials Investigator; Takeda: Other: Clinical Trials Investigator; UCB: Other: Clinical Trials Investigator. Hajek: Janssen: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Research Funding; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Consultancy, Honoraria; Pharma MAR: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Venner: BMS: Honoraria; Amgen: Research Funding; Celgene: Research Funding; Amgen: Honoraria; Takeda: Honoraria; Janssen: Honoraria; Sanofi: Honoraria; Pfizer: Honoraria. Garg: University Hospital Leicester: Current Employment; Amgen Janssen Novartis Sanofi Takeda: Honoraria; Takeda Janssen Novartis Sanofi: Other: Travel Accommodations, Expenses. Gironella Mesa: BMS, Janssen: Honoraria. Jurczyszyn: Janssen-Cilag, Amgen: Honoraria, Speakers Bureau. Robak: Biogen, Abbvie, Octapharma, Janssen: Honoraria, Other: Advisory board; AstraZeneca, Abbvie, Janssen, Octapharma, Gilead,Oncopeptides AB, Pharmacyclics, Pfizer, GlaxoSmithKline, Biogen: Research Funding; Medical University of Lodz: Current Employment. Galli: BMS, Celgene, Janssen, Sanofi, Takeda: Honoraria. Radinoff: Janssen, Pfizer, Novartis, Servier etc.: Consultancy, Honoraria; Amgen, Bayer, Takeda, etc.: Research Funding; the Bulgarian Minister of Health: Membership on an entity's Board of Directors or advisory committees. Liberati: abbvie, amgen, archigen, beigene, BMS, celgene, DR REDDY'S LABORATORIES SPA, fibrogen, glaxo, Janssen, Karyopharm, Morphosys, Novartis, Onconova, Oncopeptides ab, Roche, Sanophi, Secura Bio, Takeda, Verastem,: Research Funding. Quach: Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Antengene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen/Cilag: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol Myers Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Karyopharm: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; CSL: Consultancy, Membership on an entity's Board of Directors or advisory committees. Bila: Takeda, AMGEN, Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Katodritou: GSK, Amgen, Karyopharm, Abbvie, Janssen-Cilag, Genesis Pharma, Sanofi: Honoraria, Research Funding. DeCastro: Karyopharm: Current Employment, Current equity holder in publicly-traded company. Chai: Karyopharm: Current Employment. Van Domelen: Karyopharm: Current Employment, Current equity holder in publicly-traded company. Mishal: Karyopharm: Current Employment. Bentur: Karyopharm Therapeutics: Current Employment, Current equity holder in publicly-traded company. Shah: Karyopharm: Current Employment. Shacham: Karyopharm: Current Employment, Current equity holder in publicly-traded company, Patents & Royalties: (8999996, 9079865, 9714226, PCT/US12/048319, and I574957) on hydrazide containing nuclear transport modulators and uses, and pending patents PCT/US12/048319, 499/2012, PI20102724, and 2012000928) . Kauffman: Karyopharm Therapeutics Inc.: Current Employment, Current equity holder in publicly-traded company. Richardson: GlaxoSmithKline: Consultancy; Sanofi: Consultancy; AstraZeneca: Consultancy; Regeneron: Consultancy; Karyopharm: Consultancy, Research Funding; Janssen: Consultancy; AbbVie: Consultancy; Protocol Intelligence: Consultancy; Secura Bio: Consultancy; Takeda: Consultancy, Research Funding; Celgene/BMS: Consultancy, Research Funding; Oncopeptides: Consultancy, Research Funding; Jazz Pharmaceuticals: Consultancy, Research Funding.

Introduction: Patients with multiple myeloma (MM) have a high rate of relapse resulting in a need for multiple lines of therapy. In contrast to MM with standard risk cytogenetics (SR-Cyto), high-risk cytogenetics (HR-Cyto) in MM such as del(17p), t(4;14), t(14;16), and gain(1q) (≥3 copies), can result in shorter progression-free survival (PFS) and overall survival (OS) with less durable responses. Treatment regimens that can overcome the negative effect of HR-Cyto abnormalities are required to address this area of unmet medical need. Exportin 1 (XPO1), is overexpressed in many hematologic and solid tumor malignancies including MM, and exports tumor suppressor proteins from the nucleus to the cytoplasm, leading to their inactivation. Elevated levels of XPO1 are correlated with more aggressive MM and resistance to therapy and confers a poor prognosis. The potent oral XPO1 inhibitor, selinexor, has been approved as a triplet combination with bortezomib and dexamethasone for previously-treated MM. In the Phase 3 BOSTON study, treatment with XVd in patients with previously treated MM significantly prolonged median PFS and improved the overall response rate (ORR), with a trend towards a prolonged OS amongst all patients as well as those with HR cytogenetics. Methods: We performed post hoc analyses on patients with previously-treated MM from the XVd arm of the Phase 1b/2 study STOMP (NCT02343042) and the Phase 3 BOSTON (NCT03110562) study to determine the effects of cytogenetic abnormalities on outcomes. The HR-Cyto group included patients with at least one of the following cytogenetic abnormalities at initial diagnosis or screening: del(17p), t(4;14), t(14;16), or gain(1q) (≥3 copies). Efficacy was based on independent review committee. Results: A total of 106 patients with HR-Cyto were identified, including del(17p) (n=25), t(4;14) (n=25), t(14;16) (n=10), and gain(1q) (n=80). There were 131 patients classified as SR-Cyto including those with unknown cytogenetics. Baseline demographics were similar between groups with median age of 66 years old (range 40-87). Patients with HR-Cyto had a median PFS of 12.9 months and patients with SR-Cyto had a median PFS of 16.6 months; PFS on the BOSTON Vd control arm were 8.6 and 9.5 months with HR- and SR-Cyto, respectively. Of the individual abnormalities, a PFS of 13.2 and 13.9 months was observed in the t(4;14) and gain1q subgroups, respectively. Of the HR-Cyto subgroups with more than 10 patients, a similar median OS was observed in comparison to SR-Cyto and ranged from 20.4 months to not reached. The response of XVd treatment was maintained across HR-Cyto risk subgroups, with an ORR of 76.4% overall and the following values for subgroups: del(17p) (72.0%), t(4;14) (88.0%), and gain1q (73.8%). The ORR of the SR group was 69.5%. Of all patients that received XVd, there were 6 CRs (5.7%) and 32 VGPRs (30.2%) in the HR group and 9 CRs (6.9%) and 29 VGPRs (22.1%) in the SR group. The ORRs on the BOSTON Vd control arm were 57.7% and 64.7% for HR- and SR-Cyto, respectively. The rates of the most common treatment emergent adverse events (TEAEs) of any grade were similar across risk groups (HR- vs SR-Cyto): thrombocytopenia (65.1% vs. 54.2%), nausea (53.8% vs. 53.4%), fatigue (47.2% vs. 45.0%) decreased appetite (37.7% vs. 42.0%) and anemia (34.6% vs 40.5%). Rates of AEs of any grade peripheral neuropathy (PN) were 35.8% overall, 40.0% in del(17p), t(4;14) (40.0%), t(14;16) (30.0%), gain(1q) (38.8%), and 23.7% in the SR group. The rates of PN in the HR and SR groups of the XVd arm of the BOSTON and STOMP studies were 37.1% and 29.6% and 11.1% and 15.2%, respectively. The corresponding rates for Vd alone in the BOSTON study were 48.6% and 47.0%. Conclusions: Patients with MM with HR-Cyto treated with XVd demonstrated a comparable ORR and PFS, with a manageable safety profile compared to patients with SR-Cyto, supporting the use of XVd in patients with any cytogenetic profile. These results are consistent with the distinct and broad mechanism of action associated with XPO1 inhibition and the use of the agent in earlier lines of therapy. Further assessment of selinexor in combination with other therapies in patients with MM across the entire cytogenetic spectrum is warranted. Figure 1 Figure 1. Disclosures Bahlis: Sanofi: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; GlaxoSmithKline: Consultancy, Honoraria; Genentech: Consultancy; BMS/Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria. Richard: Karyopharm, Janssen: Honoraria. White: Amgen, Antengene, BMS/Celgene, Forus, GSK, Janssen, Karyopharm, Sanofi, Takeda: Consultancy, Honoraria. Chen: Gilead: Research Funding; BMS, Janssen, Abbvie, Novartis, Gilead, AstraZeneca: Consultancy. Delimpasi: Amgen: Honoraria, Speakers Bureau; Janssen: Honoraria, Speakers Bureau; Takeda: Honoraria, Speakers Bureau. Sutherland: Amgen: Consultancy; Janssen: Consultancy, Research Funding; GSK: Research Funding; Celgene: Consultancy; Karyopharm: Research Funding. Sebag: Janssen: Research Funding; Bristol Myers-Squibb: Consultancy, Honoraria; Karyopharm Therapeutics: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria. Gavriatopoulou: GSK: Honoraria; Janssen: Honoraria; Takeda: Honoraria; Genesis: Honoraria; Sanofi: Honoraria; Karyopharm: Honoraria; Amgen: Honoraria. Lentzsch: Oncopeptides: Consultancy; Sanofi: Consultancy, Research Funding; Karyopharm: Consultancy, Research Funding; Takeda: Consultancy; GSK: Consultancy; AbbVie: Consultancy; Celularity: Consultancy; Janssen: Consultancy; Caelum Biosciences: Consultancy, Current holder of individual stocks in a privately-held company; Ossium Health: Consultancy; Magenta Therapeutics: Current equity holder in publicly-traded company; Kadmon: Current equity holder in publicly-traded company. Chari: Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sanofi Genzyme: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Research Funding; Oncopeptides: Consultancy, Membership on an entity's Board of Directors or advisory committees; Karyopharm: Consultancy, Membership on an entity's Board of Directors or advisory committees; Secura Bio: Consultancy, Membership on an entity's Board of Directors or advisory committees; Shattuck Labs: Consultancy, Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Research Funding; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; GlaxoSmithKline: Consultancy, Membership on an entity's Board of Directors or advisory committees; Millenium/Takeda: Consultancy, Research Funding; Pharmacyclics: Research Funding; Janssen Oncology: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS/Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Antengene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding. Kriachok: Takeda, Roche, Abbvie, Janssen, MSD, Pfizer: Honoraria, Speakers Bureau; Takeda, Roche, Abbivie, Janssen, MSD: Consultancy. Dimopoulos: BMS: Honoraria; Janssen: Honoraria; Amgen: Honoraria; Takeda: Honoraria; Beigene: Honoraria. Auner: Janssen: Speakers Bureau; Amgen: Research Funding; Takeda, Karyopharm: Other: Advisory role. Leleu: Bristol-Myers Squibb: Honoraria; Carsgen Therapeutics Ltd: Honoraria; Celgene: Honoraria; Gilead Sciences: Honoraria; Janssen-Cilag: Honoraria; Karyopharm Therapeutics: Honoraria; Merck: Honoraria; Mundipharma: Honoraria; Novartis: Honoraria; Oncopeptides: Honoraria; Pierre Fabre: Honoraria; Roche: Honoraria; Sanofi: Honoraria; Amgen: Honoraria; AbbVie: Honoraria; Takeda: Honoraria, Other: Non-financial support. Usenko: Janssen: Consultancy, Honoraria, Other: Clinical Trials Investigator; AbbVie: Consultancy, Honoraria, Other: Clinical Trials Investigator; Pfizer: Consultancy, Honoraria; Acerta: Other: Clinical Trials Investigator; Ascentage: Other: Clinical Trials Investigator; Celgene: Other: Clinical Trials Investigator; Il-Yang: Other: Clinical Trials Investigator; Karyopharm: Other: Clinical Trials Investigator; Oncopeptides: Other: Clinical Trials Investigator; Rigel: Other: Clinical Trials Investigator; Takeda: Other: Clinical Trials Investigator; UCB: Other: Clinical Trials Investigator. Hajek: Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharma MAR: Consultancy, Honoraria; Novartis: Consultancy, Research Funding; AbbVie: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding. Venner: Janssen: Honoraria; Amgen: Honoraria; Takeda: Honoraria; Celgene: Research Funding; Amgen: Research Funding. Garg: Takeda Janssen Novartis Sanofi: Other: Travel Accommodations, Expenses; Amgen Janssen Novartis Sanofi Takeda: Honoraria; University Hospital Leicester: Current Employment. Quach: Antengene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen/Cilag: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Karyopharm: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol Myers Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; CSL: Consultancy, Membership on an entity's Board of Directors or advisory committees. Jagannath: Karyopharm Therapeutics: Consultancy; Bristol Myers Squibb: Consultancy; Legend Biotech: Consultancy; Janssen Pharmaceuticals: Consultancy; Sanofi: Consultancy; Takeda: Consultancy. Moreau: Celgene BMS: Honoraria; Sanofi: Honoraria; Janssen: Honoraria; Abbvie: Honoraria; Amgen: Honoraria; Oncopeptides: Honoraria. Levy: Takeda, Celgene, Seattle Genetics, AbbVie, Jazz Pharmaceuticals, Gilead Sciences, Bristol-Myers Squibb, Amgen, Spectrum Pharmaceuticals,Janssen.: Consultancy. Badros: J&J: Research Funding; Janssen: Research Funding; BMS: Research Funding; GlaxoSmithKline: Research Funding. Anderson: Celgene, BMS, Janssen, GSK, Karyopharm, Oncopeptides, Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Mateos: Oncopeptides: Honoraria; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sea-Gen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene - Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologies: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Regeneron: Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Honoraria; Bluebird bio: Honoraria; AbbVie: Honoraria; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Honoraria, Membership on an entity's Board of Directors or advisory committees. Cavo: AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; GlaxoSmithKline: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Adaptive Biotechnologies: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Accommodations, Speakers Bureau; Novartis: Honoraria; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES, Speakers Bureau; Bristol-Myers Squib: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. DeCastro: Karyopharm: Current Employment, Current equity holder in publicly-traded company. Chai: Karyopharm: Current Employment. Van Domelen: Karyopharm: Current Employment, Current equity holder in publicly-traded company. Mishal: Karyopharm: Current Employment. Bentur: Karyopharm Therapeutics: Current Employment, Current equity holder in publicly-traded company. Shah: Karyopharm: Current Employment. Shacham: Karyopharm: Current Employment, Current equity holder in publicly-traded company, Patents & Royalties: (8999996, 9079865, 9714226, PCT/US12/048319, and I574957) on hydrazide containing nuclear transport modulators and uses, and pending patents PCT/US12/048319, 499/2012, PI20102724, and 2012000928) . Kauffman: Karyopharm Therapeutics Inc.: Current Employment, Current equity holder in publicly-traded company. Richardson: Secura Bio: Consultancy; Sanofi: Consultancy; AstraZeneca: Consultancy; Oncopeptides: Consultancy, Research Funding; Janssen: Consultancy; Protocol Intelligence: Consultancy; Takeda: Consultancy, Research Funding; Regeneron: Consultancy; Celgene/BMS: Consultancy, Research Funding; GlaxoSmithKline: Consultancy; AbbVie: Consultancy; Karyopharm: Consultancy, Research Funding; Jazz Pharmaceuticals: Consultancy, Research Funding.

Introduction: Despite recent advances, there remains an unmet need for novel therapies to improve outcomes and abrogate the adverse effects of high-risk cytogenetics in patients with multiple myeloma (MM). In patients with triple class refractory MM in the Phase 2b STORM study, the clinical benefit of selinexor plus low dose dexamethasone (sel-dex) was preserved across high-risk cytogenetic subgroups, supporting further evaluation of selinexor combined with other anti-MM therapies (Nooka et al. ASH 2019). The phase 3 BOSTON study evaluated the combination of weekly sel-dex with the proteasome inhibitor (PI) bortezomib (SVd) against standard twice weekly bortezomib-dex (Vd) in patients with MM who had received 1-3 prior therapies. SVd significantly improved progression free survival (PFS), time to next therapy (TTNT), overall response rate (ORR) and depth of response (≥VGPR), while inducing less overall and grade ≥2 peripheral neuropathy (PN) compared with Vd. Here, we present the results of prespecified subgroup analyses from the BOSTON study according to cytogenetic risk status. Methods: In the BOSTON study, patients were randomly assigned (1:1) to once weekly oral sel (100 mg) plus once weekly subcutaneous (SC) bortezomib (1.3 mg/m2) and dex (20 mg BIW) in the SVd arm or twice weekly SC bortezomib (1.3 mg/m2) and dex (20 mg QIW) in the Vd arm. Treatment was administered in both arms until disease progression. The primary endpoint was PFS, as assessed by an Independent Review Committee (IRC). Central FISH analyses were performed on CD138+ sorted cells from bone marrow aspirates collected at screening. The high-risk group consisted of patients with at least 1 of the following abnormalities: del(17p), t(4;14), t(14;16), and amplification of 1q21 in ≥10% of screened plasma cells with amp (1q21) requiring ≥3 copies. The standard-risk group consisted of all other patients with available and known baseline cytogenetics. Results: Of the 402 enrolled patients, 192 (48%) had high-risk (SVd=97, Vd=95) and 210 (52%) had standard-risk (SVd=98, Vd=112) cytogenetics. Baseline patient and disease characteristics were well balanced across treatment arms. SVd significantly improved PFS relative to Vd in the high-risk (12.9 vs 8.1 months; HR, 0.67; 95% CI, 0.45-0.98; P=0.0192) and standard-risk (16.6 vs 9.7 months; HR, 0.63; 95% CI, 0.42-0.95; P=0.0131) groups. Time to next treatment was significantly increased with SVd in the high-risk (14.6 vs 8.7 months; P=0.0049) and standard risk groups (NR vs 13.1 months; P=0.0158). The ORR was significantly improved with SVd in the high-risk group (77.3% vs 55.8%; P=0.0008) and numerically improved in the standard-risk group (75.5% vs 67.9%; P=0.11) with comparable rates between the high-risk and standard-risk groups in the SVd arm. Very good partial response or better was achieved in 42.3% patients on SVd versus 24.2% on Vd (P=0.0041) and 46.9% on SVd versus 39.3% on Vd (P=0.13) in the high-risk and standard-risk groups, respectively. Overall survival was 23.5 months in the high-risk group in the Vd arm and was not reached in the other groups. Efficacy by specific cytogenetics abnormalities in the high-risk subgroup is shown in the table below. PFS and ORR were improved with SVd compared with Vd across all subgroups except t(14;16) which was the smallest subgroup (N=18, 4% of the study population). There were 61 deaths in the high-risk group (SVd=27 and Vd=34) versus 48 in the standard-risk group (SVd=20 and Vd=28). The safety profiles of SVd and Vd in the high-risk and standard-risk groups were consistent with the overall population. Rate of grade ≥2 peripheral neuropathy was lower with SVd compared with Vd in both the high-risk (26.8% vs 32.3%; P=0.18) and standard-risk groups (15.3% vs 36.0%; P=0.0003). Conclusions: These prespecified subgroup analyses from the BOSTON study demonstrate that despite utilizing 40% less bortezomib and 25% less dexamethasone during the first 24-weeks of treatment, SVd is superior to Vd in patients with MM including high-risk patients. The PFS benefit was particularly notable in patients with del(17p), t(4;14) and amp(1q21) abnormalities. The ORR was comparable between the high-risk and standard-risk groups in the SVd arm. These data support the use of selinexor, with its novel mechanism of action, in the treatment of patients with early relapsed MM, including those with high risk cytogenetic abnormalities. Figure 1 Disclosures Chari: Secura Bio: Consultancy; Novartis: Honoraria; Seattle Genetics: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Oncopeptides: Consultancy; Adaptive Biotechnology: Honoraria; The Binding Site: Honoraria; Bristol Myers Squibb: Consultancy; Pharmacyclics: Research Funding; Sanofi Genzyme: Consultancy; Karyopharm: Consultancy; Celgene: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Antengene: Consultancy; Amgen: Consultancy, Research Funding; Array BioPharma: Honoraria; Glaxo Smith Kline: Consultancy. Delimpasi:GENESIS: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Amgen: Consultancy, Honoraria. Spicka:Celgene, Amgen, Janssen-Cilag, Takeda, Bristol-Myers Squibb, Novartis, Sanofi: Consultancy, Honoraria, Speakers Bureau. Kryachok:Takeda, Janssen: Consultancy; Janssen, Bayer, Karyopharm, MSD, Acerta, AvbbVie, Debiopharm: Research Funding; Takeda, Janssen, Novartis, Roche, MSD, Bayer: Consultancy, Research Funding; Takeda, MSD, AbbVie, Ro: Other: Travel, accommodations, expenses. Dimopoulos:BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, Research Funding, Speakers Bureau. Auner:Karyopharm: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria. Leleu:Oncopeptide: Honoraria; Incyte: Honoraria; Merck: Honoraria; Carsgen: Honoraria; Amgen: Honoraria; Karyopharm: Honoraria; Sanofi: Honoraria; GSK: Honoraria; AbbVie: Honoraria; Janssen: Honoraria; BMS-celgene: Honoraria; Novartis: Honoraria. Hajek:Novartis: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharma MAR: Consultancy, Honoraria; BMS: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Roche: Consultancy, Honoraria, Research Funding; Oncopeptides: Consultancy, Honoraria, Research Funding. Sinha:Dr Reddys Lab, Intas Pharmaceuticals, Karyopharm Therapeutics: Honoraria. Venner:Janssen, BMS/Celgene, Sanofi, Takeda, Amgen: Honoraria; Celgene, Amgen: Research Funding. Garg:Janssen, Takeda, Celgene, Novartis, Sanofi: Honoraria. Stevens:Amgen, MorphoSys: Consultancy. Quach:GlaxoSmithKline, Karyopharm, Amgen, Celgene, Janssen Cilag: Honoraria; GlaxoSmithKline, Karyopharm, Amgen, Celgene, Janssen Cilag: Consultancy; Amgen, Celgene, karyopharm, GSK, Janssen Cilag, Sanofi.: Membership on an entity's Board of Directors or advisory committees; Amgen, sanofi, celgene, Karyopharm, GSK: Research Funding. Jagannath:Takeda: Consultancy, Honoraria; Legend Biotech: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria. Moreau:Amgen: Consultancy, Honoraria; Celgene/Bristol-Myers Squibb: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Takeda: Honoraria; Sanofi: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Novartis: Honoraria. Levy:Bristol Meyers Squibb: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Karyopharm: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy, Honoraria, Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding; BeiGene: Consultancy, Research Funding, Speakers Bureau; Baylor University Med Center: Current Employment; Amgen: Consultancy, Honoraria, Research Funding; AstraZeneca: Consultancy, Honoraria, Research Funding. Badros:University of Maryland: Current Employment; Amgen: Consultancy. Anderson:Amgen: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria, Research Funding; GSK: Consultancy, Honoraria, Research Funding; Karyopharm: Consultancy, Honoraria, Research Funding. Bahlis:Sanofi: Consultancy, Honoraria; Karyopharm Therapeutics: Consultancy, Honoraria; Genentech: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria; GSK: Consultancy, Honoraria; BMS/Celgene and Janssen: Consultancy, Honoraria, Other: Travel, Accomodations, Research Funding; Takeda: Consultancy, Honoraria; Amgen: Consultancy, Honoraria. Facon:Celgene, Janssen, Takeda, Amgen, Roche, Karyopharm, Oncopeptides, BMS, Sanofi: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Mateos:Janssen-Cilag: Consultancy, Honoraria; Abbvie/Genentech: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologies: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; PharmaMar-Zeltia: Consultancy; Oncopeptides: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Regeneron: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Consultancy; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Cavo:AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel accomodations, Speakers Bureau; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; GlaxoSmithKline: Honoraria, Speakers Bureau; Karyopharm: Honoraria; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel accomodations, Speakers Bureau; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Chang:Karyopharm Therapeutics Inc: Current Employment. Landesman:Karyopharm Therapeutics Inc: Current Employment, Current equity holder in publicly-traded company. Joshi:Karyopharm Therapeutics Inc: Consultancy. Chai:Karyopharm Therapeutics Inc: Current Employment. Arazy:Karyopharm Therapeutics Inc.: Current Employment. Shah:Karyopharm Therapeutics Inc: Current Employment, Current equity holder in publicly-traded company. Shacham:Karyopharm: Current Employment, Current equity holder in publicly-traded company, Patents & Royalties: (8999996, 9079865, 9714226, PCT/US12/048319, and I574957) on hydrazide containing nuclear transport modulators and uses, and pending patents PCT/US12/048319, 499/2012, PI20102724, and 2012000928) . Kauffman:Karyopharm Therapeutics Inc: Current Employment, Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees. Richardson:Celgene/BMS, Oncopeptides, Takeda, Karyopharm: Research Funding.

Introduction:Sickle cell disorders were originally found in the African regions, Arabian Peninsula and parts of India. However, in today's age of globalization patients with homozygous or compound heterozygous Sickle cell disorders can be found all over the world. The objective of our study was to assess the distribution and clinical presentation of patients with Sickle homozygous or heterozygous diseases in the Eastern part of India. Methods:Patients who attended the Thalassemia Clinic in our tertiary care center, between 1st January 2018 to 31st May 2020 (2 years and 4 months) were retrospectively analysed and the ones with a component of Sickle haemoglobin(HbS), either in the form of Sickle cell anemia/homozygous Sickle cell disorders(SCA) or compound heterozygous diseases, like Sickle cell/β thalassemia(HbS/β), Sickle cell/Delta thalassemia(HbS/D), Sickle cell Haemoglobin/E thalassemia(HbS/E), were included in the study. People having Sickle cell trait (HbS trait), have also been included. Thorough history of painful crises, blood transfusions, family history and treatment history was elicited and every patient was clinically examined. The patients were diagnosed by High Pressure Liquid Chromatography (HPLC) or Thalassemia Mutation analysis by Polymerase Chain reaction (PCR). Results:A total of 95 patients with a component of HbS were considered as our study cohort, with HbS/β thalassemia patients being the majority (53.7%), followed by SCA (30.5%). Age of the study cohort ranged between 2-50 years age. HbS/β thalassemia patients presented at a later age (median 17.5 years) than SCA patients (median 12 years). Their demographic distribution is depicted in Table 1. The most common clinical presentation was painful crisis (32,33.7%), be it abdominal pain (11,11.6%) or bone pain (13,13.7%). Other presenting complaints were pallor (26,27.4%), jaundice (12,12.6%) and fever (4,4.2%). Some rarer presenting manifestations were fatigue (4,4.2%), splenic infarction (1,1%), convulsions (1,1%), Raynaud's phenomenon (1,1%), headache (1,1%) or itchy skin lesions (1,1%). Few patients (4,4.2%) had recurrent pregnancy loss, and one patient was diagnosed incidentally during an antenatal check-up. Most patients had more than one complaint. Very occasionally patients required hospital admission, the reasons being, chest pain, fever, convulsions or abdominal pain. HbS trait was diagnosed incidentally during evaluation for other illnesses, most commonly during evaluation of pallor (3,60%): one patient was later diagnosed with iron deficiency anemia. Most patients who attended our center were from within the state or neighbouring states. The patients were treated with Hydroxyurea, with/without blood transfusions, chelation therapy with Deferasirox as required and Folic acid supplementation. People with HbS Trait continued to receive Folate supplementation. Discussion and Conclusions:This study highlights the varied distribution of HbS among the population attending a tertiary care center, irrespective of a specific area-based population. Till date most studies conducted in India have highlighted the prevalence of Sickle cell disorders among specific focused populations. HbS/β thalassemia was the most common sickle cell disorder in our study. This is in contrast to most findings in published literature from other countries, where SCA is the commonest. Only one other study conducted in eastern India, has depicted a finding similar to ours. The median age of disease presentation was at a later age in our study, in contrast to findings in published literature from other countries. There is a variation in the severity of disease manifestation in our study cohort. The most common painful crisis was bone pain, followed by abdominal pain. Pallor was also one of the commonest presenting symptoms. Stroke, a common manifestation of SCA in other countries, was rare in our study cohort. Disclosures No relevant conflicts of interest to declare.

Introduction: Treatment of older or frail patients (pts) with multiple myeloma (MM) remains challenging due to impaired organ function, underlying comorbidities, need for convenient regimens and burden of care, all of which impact the tolerability of anti-MM therapies. In the STORM study, selinexor plus dexamethasone (sel-dex) demonstrated anti-MM activity with an ORR of 26.2% and similar safety across all age groups in pts with triple-class refractory MM (Chari et al. NEJM 2019, Gavriatopoulou et al. IMW 2019). In the phase 3 BOSTON study, the combination of weekly sel-dex with once weekly bortezomib (SVd) was superior to standard twice weekly bortezomib and dex (Vd) across all efficacy endpoints in pts with MM who had received 1-3 prior therapies. Furthermore, while conferring a longer PFS and higher ORR than Vd, SVd was associated with significantly reduced rates of peripheral neuropathy (PN), the most clinically relevant toxicity associated with bortezomib that limits long term administration, especially in older and/or frail pts. Here we present results of subgroup analyses of the BOSTON study to evaluate the safety and efficacy of SVd versus Vd based on age and frailty index. Methods: Pts enrolled in BOSTON were assigned (1:1) to once weekly oral sel (100 mg) plus once weekly subcutaneous (SC) bortezomib (1.3 mg/m2) and dex (20 mg BIW) in the SVd arm or to standard twice weekly SC bortezomib (1.3 mg/m2) and dex (20 mg QIW) in the Vd arm. Treatment was administered in both arms until disease progression. The primary endpoint was PFS, as assessed by an Independent Review Committee. For these analyses, pts were assigned to 2 groups based on age ( Results: Of the 402 enrolled pts, 241 (60%) were ≥65 years (SVd=109, Vd=132). Of these, 81 (37%) were ≥75 and 106 (44%) were categorized as frail (SVd=51, Vd=55). Baseline pt and disease characteristics were well balanced between treatment arms in the subgroups. PFS was prolonged in both age groups with SVd compared with Vd. In ≥65, PFS was 21.0 vs 9.5 months (HR, 0.55; 95% CI, 0.37-0.83; P=0.0018) and in Conclusions: In pts with previously treated MM, the once weekly SVd regimen led to prolonged PFS, improved response rates and rates of PN regardless of age and frailty score compared to standard twice weekly Vd. Non-PN AEs were higher with triplet than doublet therapy, but most of the AEs were reversible and treatable. There were fewer deaths on SVd in pts ≥65 and in frail pts compared to Vd. Once weekly SVd is a potent and convenient treatment option for pts with previously treated MM, including those who are ≥65 years and/or frail. Figure Disclosures Auner: Karyopharm: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Research Funding. Gavriatopoulou:Amgen: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Genesis Pharma: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria. Delimpasi:GENESIS: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Amgen: Consultancy, Honoraria. Spicka:Celgene, Amgen, Janssen-Cilag, Takeda, Bristol-Myers Squibb, Novartis, Sanofi: Consultancy, Honoraria, Speakers Bureau. Dimopoulos:BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, Research Funding, Speakers Bureau. Leleu:Incyte: Honoraria; Merck: Honoraria; AbbVie: Honoraria; Carsgen: Honoraria; Janssen: Honoraria; Novartis: Honoraria; BMS-celgene: Honoraria; Amgen: Honoraria; GSK: Honoraria; Sanofi: Honoraria; Karyopharm: Honoraria; Oncopeptide: Honoraria. Hajek:Celgene: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria, Research Funding; Pharma MAR: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Roche: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Oncopeptides: Consultancy, Honoraria, Research Funding. Sinha:Dr Reddys Lab, Intas Pharmaceuticals, Karyopharm Therapeutics: Honoraria. Venner:Janssen, BMS/Celgene, Sanofi, Takeda, Amgen: Honoraria; Celgene, Amgen: Research Funding. Garg:Janssen, Takeda, Celgene, Novartis, Sanofi: Honoraria. Stevens:Amgen, MorphoSys: Consultancy. Quach:Amgen, Celgene, karyopharm, GSK, Janssen Cilag, Sanofi.: Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline, Karyopharm, Amgen, Celgene, Janssen Cilag: Honoraria; Amgen, sanofi, celgene, Karyopharm, GSK: Research Funding; GlaxoSmithKline, Karyopharm, Amgen, Celgene, Janssen Cilag: Consultancy. Jagannath:Sanofi: Consultancy, Honoraria; Legend Biotech: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; BMS: Consultancy, Honoraria. Moreau:Sanofi: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Takeda: Honoraria; Abbvie: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Celgene/Bristol-Myers Squibb: Consultancy, Honoraria; Novartis: Honoraria. Levy:Takeda: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy, Honoraria, Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; Karyopharm: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Bristol Meyers Squibb: Consultancy, Honoraria, Research Funding; AstraZeneca: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding; BeiGene: Consultancy, Research Funding, Speakers Bureau; Baylor University Med Center: Current Employment. Badros:Amgen: Consultancy; University of Maryland: Current Employment. Anderson:BMS: Consultancy, Honoraria, Research Funding; Karyopharm: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; GSK: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding. Bahlis:BMS/Celgene and Janssen: Consultancy, Honoraria, Other: Travel, Accomodations, Research Funding; Takeda: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Genentech: Consultancy, Honoraria; GSK: Consultancy, Honoraria; Karyopharm Therapeutics: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria. Facon:Celgene, Janssen, Takeda, Amgen, Roche, Karyopharm, Oncopeptides, BMS, Sanofi: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Mateos:EDO Mundipharma: Honoraria; Seattle Genetics: Honoraria; Abbvie: Honoraria; Janssen: Honoraria; Bristol-Myers Squibb: Honoraria; Amgen: Honoraria; GlaxoSmithKline: Honoraria; Adaptive Biotechnologies: Honoraria; Takeda: Honoraria; Roche: Honoraria. Cavo:Jannsen, BMS, Celgene, Sanofi, GlaxoSmithKline, Takeda, Amgen, Oncopeptides, AbbVie, Karyopharm, Adaptive: Consultancy, Honoraria. Joshi:Karyopharm Therapeutics Inc: Consultancy. Chai:Karyopharm Therapeutics Inc: Current Employment. Arazy:Karyopharm Therapeutics Inc.: Current Employment. Shah:Karyopharm Therapeutics Inc: Current Employment, Current equity holder in publicly-traded company. Shacham:Karyopharm: Current Employment, Current equity holder in publicly-traded company, Patents & Royalties: (8999996, 9079865, 9714226, PCT/US12/048319, and I574957) on hydrazide containing nuclear transport modulators and uses, and pending patents PCT/US12/048319, 499/2012, PI20102724, and 2012000928) . Kauffman:Karyopharm Therapeutics Inc: Current Employment, Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees. Richardson:Celgene/BMS, Oncopeptides, Takeda, Karyopharm: Research Funding.

8019 Background: Multiple myeloma (MM) typically affects older populations, which are more vulnerable to toxicity with anti-MM treatments. These patients (pts) have significant morbidity and mortality, resulting in a need for dose modifications or alternative suboptimal treatment options. Significant improvements were observed in the BOSTON study with XVd vs Vd in median progression-free survival (PFS), overall response rate (ORR), and rates of peripheral neuropathy (PN); median overall survival (OS) trended in favor of XVd. Methods: The phase 3 randomized BOSTON trial (NCT03110562) is a controlled, open-label study of once weekly XVd vs. twice weekly standard Vd in pts with MM and 1-3 prior treatment regimens. We performed post-hoc analyses to compare survival benefits in pts ≥65 vs < 65 years of age. Results: The BOSTON study enrolled a total of 402 pts between June 2017 and February 2019 that were randomized into XVd or Vd arms. The numbers of pts treated with XVd or Vd who were ≥65 were 109/132 and 86/75 who were < 65, respectively. Baseline characteristics were similar by age although pts ≥65 years were less likely to have received ASCT than those < 65 years (48.4% vs. 25.3%). Median PFS was prolonged with XVd compared with Vd, across both age groups: ≥65 (HR, 0.55 [95% CI, 0.37-0.83] P = 0.002) and < 65, (HR, 0. 74 [95% CI, 0.49-1.11], P = 0.07). Vd was associated with a lower ORR (64.4%) than treatment with XVd (76.1%) (OR, 1.77 [95% CI, 1.00-3.11], P = 0.024) in pts ≥65, while the ORR in those < 65 was 76.7% with XVd and 58.7% (OR, 2.33 [95% CI, 1.18-4.59], P = 0.007) with Vd. As of Jan 2021, the median OS for the overall population was not reached for both arms (HR = 0.86; p = 0.193), with 61 and 75 deaths in the XVd and Vd arms, respectively. Median OS was not reached in pts ≥65 with XVd and was 28.6 months with Vd (HR = 0.60; 95% CI, 0.38-0.94; p = 0.012), while there was no difference in the OS for pts < 65 (HR = 1.52; 95% CI, 0.86-2.68; p = 0.926). Pts ≥65 had a lower incidence of death with XVd as compared to Vd (29 vs 56) and there were 32 deaths with XVd and 19 with Vd in pts < 65. Grade ≥3 treatment-emergent adverse events were not observed more often in older compared to younger pts. Amongst pts ≥65, PN of any grade was lower with XVd (32.1%) compared to Vd (46.5%); (OR 0.57 [95% CI 0.34-0.97], p = 0.017), including a lower incidence of grade ≥3 PN (XVd 4.6% vs. Vd 11.6%). Pts < 65 followed a similar trend of PN AEs of any grade: XVd, 32.6%; Vd, 48.0% (OR 0.42 [95% CI 0.21-0.82], p = 0.006). Conclusions: In an older patient population with a poor prognosis, XVd was associated with a significant survival benefit, improved PFS and OR with reduced PN, and requires relatively short and infrequent clinic visits. XVd may be a simple, effective regimen for pts ≥65 years of age. Clinical trial information: NCT03110562.

Hemoglobin (Hb)-F inducers are known to improve Hb level and transfusion dependence in thalassemia. This pilot study was conducted to assess the efficacy and safety of Hb-F inducer thalidomide compared to hydroxyurea (HU) in Hb E-β thalassemia patients.This was a prospective interventional single-centre study with 45 Hb E-beta thalassemia patients equally divided into group-I (thalidomide+folic acid), group-II (HU + folic acid) and group-III (folic acid). Response was assessed at various time intervals with 12-months follow up period. Primary end points were increment in Hb, Hb-F level and improvement in transfusion requirement; secondary end point were tolerability and safety.There was 100% responder (R: Hb-increment ≥1 g/dl) in group-I with 66.67% major responder (MaR: Hb-increment ≥2 g/dl), while there were 40% and 0% responder in group-II and III respectively. Hb-increment was significantly (p-value0.0001) better in thalidomide arm compared to HU. The Hb-increment was attributable to both increase in Hb-F levels and reduction in ineffective erythropoiesis in thalidomide arm. Transfusion reduction was significantly better in group-I compared to group-II (100% vs 34%). No severe adverse effects was reported by patients of any group.Thalidomide showed a persistent significant Hb-increment and transfusion independence in Hb E-β thalassemia patients compared to HU.

Background: Tribal population in West Bengal constitutes a significant proportion (5.1%) and the vulnerable group because of lower socio-economic status, poor literacy rate and malnutrition. The present study was conducted to evaluate hemoglobin level and prevalence of anemia among the tribal children from the western districts of West Bengal, India.Methods: A cross-sectional study was conducted on school going (class I to class VIII) tribal children (≥5 to

Immune suppression is a crucial pillar for treatment of aplastic anemia. Cyclosporine monotherapy is an easily available, affordable therapeutic option with good safety profile. This prospective study was conducted over a period of 2 years from June 2012 to July 2014. The diagnosis and response to treatment of aplastic anemia was established as per published criteria. Follow up was done at 3 and 6 months in order to assess the response. 57 patients of acquired aplastic anemia with median age of 37 years (6 to 81 years) were included in the study. 35 (62 %) cases were severe aplastic anemai, 16 (28 %) non severe aplastic anemia and 6 (10 %) were very severe aplastic anemia. At 3 months overall response rate (OR) was 7 (14 %) and at 6 months the OR rate of 11 (19.6 %) was achieved. Transiently raised creatinine, liver function abnormality and gum hypertrophy were the main side effects observed in this cohort. Oral cyclosporine monotherapy at dose of 5 mg/kg/day is a relatively safe treatment option for resource poor patients with aplastic anemia.

TO THE EDITOR: Primary non-Hodgkin lymphoma (NHL) of bone is a rare disorder [1]. Primary bone lymphoma involving multiple sites is even rarer and in the majority of cases, the diagnosis is diffuse large B-cell lymphoma (DLBCL). Here we report the case of a young patient with unexplained diffuse bone pain that was diagnosed as primary bone lymphoma (B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and Burkitt lymphoma) with multifocal osteolytic lesions.

Hemorrhagic joint effusions are rarely seen in patients with haemoglobinopathies. Joint effusions often develop in association with deferiprone-related arthropathy in beta thalassaemia patients. Here we report a very rare case of bilateral knee and hip joint effusions in a case of hemoglobin E (HbE) beta thalassemia patient.

Background: Rarity of rare bleeding disorders (RBDs) is attributed to very low incidence based on ethnicity, distribution and complexity of diagnostic tools. There is scarcity of data on RBDs from Eastern India. This study aims to understand the distribution of RBDs in this region for better patient care.Methods: Retrospective study conducted on patients presented with symptoms/signs of bleeding from January 2018 to December 2019 (two years). Patients having bleeding manifestations from causes other than inherited coagulation disorders, IPDs, and vWD were included. Complete haemogram, peripheral blood smear, coagulation tests, vWD assay and platelet function tests were carried out.Results: Out of 2415 patients, 1570 were included after exclusion of other diseases. Immune Thrombocytopenia (ITP) and Hemophilia being excluded, 40/1570 (2.5%) patients were found to have RBDs. Median age was 11.6 years (range, 1.25-40 years). Most common was IPDs (2.9%, n=19); Glanzmann thrombasthenia was commonest (1.5%, n=10). vWD was second (1.7%, n=11) in occurrence; vWD type-III was the commonest subtype (0.9%, n=6). ICDs comprised 1.5% (n=10) of all patients; congenital afibrinogenemia (0.6%, n=4) was most common. Other ICDs prevalent in this cohort included FVII, FV, FX and FXIII deficiencies. Most common presentations were ecchymoses or prolonged bleeding from cut injuries or menorrhagia.Conclusions: RBDs may present in varied ways and are often difficult to diagnose correctly. Distribution of RBDs in this patient cohort differs from published literature from Western studies.

8501 Background: Selinexor is an oral, selective inhibitor of XPO1-mediated nuclear export, leading to the reactivation of tumor suppressor proteins. In a phase 1b/2 study, the combination of once weekly (QW) selinexor with bortezomib and dexamethasone (SVd) was well tolerated with anti-MM activity in patients (pts) with PI-sensitive and PI-refractory disease. While twice weekly (BIW) bortezomib in combination therapy is efficacious, prolonged use is limited due to peripheral neuropathy (PN, 50-60%). The BOSTON study was designed to determine if SVd improves progression free survival (PFS), overall response rates (ORR) and reduces the rate of PN vs Vd. Methods: BOSTON is a global, phase 3, randomized study of QW SVd vs BIW Vd after 1-3 prior anti-MM regimens. The primary endpoint is PFS. Secondary endpoints include ORR, overall survival (OS) and PN (rates and EORTC QLQ-CIPN20 outcomes). Randomization is stratified by treatment with prior PI therapies, number of prior anti-MM regimens (1 vs > 1), and Revised International Staging System (R-ISS; Stage III vs I or II). Following confirmation of progressive disease, pts on Vd could cross over to either: 1) SVd for pts able to tolerate continued bortezomib or 2) selinexor and dexamethasone for pts with bortezomib intolerance. Results:402 pts were enrolled; 195 and 207 to SVd and Vd, respectively. Median age was 67 (range: 38-90). Most (59.6%) pts were > 65 years and 57.1% were male. R-ISS stage at the time of MM diagnosis was III for 18.5% of pts. Baseline characteristics were balanced across the 2 arms. SVd significantly prolonged PFS vs Vd (median 13.93 vs 9.46 months, HR = 0.70, P = 0.0066). SVd was associated with a significantly higher ORR (76.4% vs 62.3%, P = 0.0012). Median OS was not reached on SVd vs 25 months on Vd (P = 0.28). Most frequent treatment-related adverse events (grade ≥3) for SVd vs Vd were thrombocytopenia (35.9% vs 15.2%), fatigue (11.3% vs 0.5%) and nausea (7.7% vs 0%). Clinically important differences were reported on the motor, autonomic and sensory scales on CIPN20. PN rates (grade ≥2) were significantly lower with SVd vs Vd (21.0% vs 34.3%, P = 0.0013). Conclusions: BOSTON is the first phase 3 study to evaluate the clinical benefit of SVd for relapsed/refractory MM. The study met the primary endpoint: once weekly SVd significantly improved PFS and ORR compared to twice weekly Vd. Rates of PN were significantly reduced with numerically fewer deaths on SVd vs Vd. Full dataset will be presented at the meeting. Clinical trial information: NCT03110562 .

Background Burkholderia cepacia, an aerobic gram-negative bacillus, is a frequent colonizer of fluids used in the hospital ward. It poses little risk of infection to healthy people; however it is a known important opportunistic pathogen causing morbidity and mortality due to its intrinsic resistance to most of the antibiotics in hospitalized patients. Small hospital outbreaks are frequent. B. cepacia may occur as an opportunistic infection in hemato-oncology patients. Here we present an outbreak of Burkholderia cepacia infection in hematology ward of our institute. Methods Febrile episodes as defined by IDSA guideline, 2010 were followed, and blood for culture and sensitivity was sent in all the events. The culture was done by an automated method using Bactalert 3d Biomeriux & sensitivity pattern by Microscan Siemens method and subsequently detected by PCR based method. Results During September 2016 to February 2017 (six months), a total of 498 blood cultures were sent during febrile episodes. Out of which 60 (12%) came out to be positive for different microorganisms. Out of all positive cultures, Burkholderia cepacia was detected in 29 (48%) patients, which reduced drastically following the change in antibiotic administration practice. All isolates showed sensitivity to pipercillin+tazobactum, cefoperazone+sulbactum, fluoroquinolones, cotrimoxazole and carbapenems and resistance to polymyxin B and colistin. With timely intervention by appropriate intravenous antibiotics as per culture sensitivity result and change in antibiotic preparation practice, overall mortality was low 1 (4%) out of 29 culture positive episodes. Conclusion Change of antibiotic preparation practice was the key to control this outbreak, and overall mortality was low.

Interleukin-2 (alias: IL-2, TCGF, Lymphokine), a type of interleukin, is also a potent signalling molecule in the signalling cascade of the immune-mediated activation of T Lymphocytes leading to the destruction of haematopoietic stem cell (HSC) which is the basis of acquired aplastic anaemia (AAA). The objective was to study the association of IL-2 in the bone marrow plasma (BMP) and peripheral blood plasma (PBP) in AAA patients.A total of 52 BMP and PBP-paired samples (both from the same patients) was collected from the confirmed AAA patients and 10 healthy individuals. The level of IL-2 was measured by the quantitative enzyme-linked immunosorbent assay (ELISA). The Mann-Whitney U test was used for statistical analysis.Significantly increased level of IL-2 was observed in the BMP than PBP of AAA patients. The level of IL-2 in PBP and BMP was found to be very low in the control cases. Considerably increased levels of IL-2 were found in the PBP and BMP of AAA patients as compared to controls (48.54 ± 21.89 vs. 1.99 ± 1.25 p-value 0.00001) and (75.33 ± 41.9 vs. 3.12 ± 1.82; p-value 0.00001) respectively. Among these patients, the IL-2 levels were higher in patients with Very Severe Aplastic Anaemia (VSAA) and Severe Aplastic Anaemia (SAA) than those with Non-severe Aplastic Anaemia (NSAA) in the PBP (65.6 ± 23.61 vs. 31.72 ± 7.64; p-value 0.00338) and (45.37 ± 16.25 vs. 31.72 ± 7.64; p-value 0.01468) respectively. Again the IL-2 levels were higher in patients with VSAA and SAA than those with NSAA in the BMP (115.01 ± 38.91 vs. 38.32 ± 19.49; p-value 0.00001) and (66.44 ± 23.34 vs. 38.32 ± 19.49; p-value 0.0006). The IL-2 level was higher in VSAA than SAA in PBP (65.6 ± 23.61vs. 45.37 ± 16.25; p-value 0.0114) and BMP (115.01 ± 38.91 vs. 66.44 ± 23.34; p-value 0.00044).This study emphasized on the bone marrow and blood plasma levels of IL-2 in aplastic anaemia and their relationship with disease severity. The results indicate towards the fact that IL-2 may have an important association with the marrow failure of AAA patients and thus can help in disease development. Further study is necessary for better understanding.

Objectives Fanconi anaemia (FA) is a rare inherited bone marrow failure and autosomal recessive blood disorder. FA patients have a higher risk of cancer, including acute myeloid leukaemia and squamous cell carcinoma. Maximum, but not all, affected individuals have one or more somatic abnormalities, including skin, skeletal, genitourinary, gastrointestinal, cardiac and neurological anomalies, etc. Positive stress cytogenetics has immense implications for the treatment and management of FA. The aim of our study was to find out the incidence of FA in the population of phenotypically normal aplastic anaemia (AA) patients in West Bengal. Methods Ethical clearances were obtained from the corresponding institutional committees. A total of 117 AA cases was selected. Stress cytogenetics was performed from peripheral venous blood (PVB) samples of 63 AA patients (age ≤ 50 years) and 63 age- and sex-matched healthy individual (control) using Mitomycin C (MMC). Results Out of 63 AA patients, 6 (9.25%) cases showed positive stress cytogenetics suggestive of FA, which is statistically significant (p-value - 0.000532), analysed by chi-square test. Discussion A considerable percentage of patients showing sensitivity towards MMC, even if they are phenotypically normal and did not have any distinguishable features which are generally found in FA. Conclusion This observation may indicate that stress cytogenetics analysis of phenotypically normal AA patients (≤50 years) is essential for the improvement of the treatment procedure.

Polycythemia vera is a myeloproliferative disorder characterized by the overproduction of various cell lines. Bleeding, thrombotic, and vascular complications are the major causes of morbidity and mortality in polycythemia vera (PV), occurring in 40–60% of the patients. Thrombotic occlusion of large arterial vessels is also a frequent finding in PV and generally involves cerebral and coronary vessels. Here we report a 43year-old male patient suffering from PV presented with non-ST-segment elevation myocardial infarction (NSTEMI) and was treated successfully with conservative therapy.

Objectives To study any possible correlation between arsenic toxicity and the development of oral carcinoma in West Bengal population. Material and methods Ethical clearance for this study was obtained from the Vivekananda Institute of Medical Sciences. Out of 30 785 patients attending our hospital from November 2012 to July 2015, 107 cases and 50 control individuals were selected. The hair and buccal smear samples were obtained upon their consent for the purpose of the analysis of arsenic count and cytogenetic damage, respectively. Results Ninety-six percent of cases came from the highly arsenic affected districts and 81.3% showed their arsenic count above the safe limit (0.8 μg/g) whereas 96% of the controls' arsenic count was within the safe limit. The study showed a significant difference of the micronuclei and apoptosis frequency between the cases and controls. Conclusions The difference of micronuclei and apoptosis frequency between cases and controls was significant. The maximum number of cases came from highly arsenic affected areas and a higher percentage of cases showed elevated arsenic count, as compared to controls, which may indicate a possible link between arsenic toxicity and this disease. However, a larger sample size is required for a proper correlation. Int J Occup Med Environ Health 2017;30(2):271-279.

There is paucity of information from eastern India with regard to observed dominant micro-organisms causing febrile neutropenia (FN) in patients with haematological malignancies. To identify the prevalence of pathogenic microorganisms associated with FN. A total number of 268 episodes of FN were analysed from September’2010 to October’2013. The blood samples were inoculated into brain heart infusion broth, glucose broth, Hicombi dual performance media (Himedia, LQ-12) at 37° C for 168 h and Bactec method was also performed for these samples. Blood agar, chocolate agar, MacConkey’s agar and cystine lactose electrolyte deficient agar were used for isolation of the microorganisms. A total number of 78 (29.10 %) episodes revealed positive growths. Gram negative bacilli and Gram positive cocci were isolated in 61.53 and 34.61 % cases respectively. The eight commonest isolates were Pseudomonas aeruginosa (14.10 %), methicillin resistant Staphylococcus aureus (MRSA-12.82 %), Acinetobacter sps (11.53 %), coagulase negative Staphylococcus (10.25 %), Klebsiella pneumoniae (8.97 %), Escherichia coli (8.97 %), ESBL E. coli (6.41 %), methicillin sensitive S. aureus (MSSA-6.41 %). Amongst other less common isolates were Citrobacter kosseri (3.84 %), Citrobacter freundii (2.56 %), Ralstonia paucula (2.56 %), Cedecia neteri (1.28 %), methicillin resistant coagulase negative Staphylococcus (2.56 %). Candida spp. including two cases of Candida non-albicans was isolated in 3.84 % of cases. P. aeruginosa was the commonest pathogenic isolates in FN patients associated with haematological malignancies in this study. Gram negative bacteria were the commonest isolates in FN including significant numbers of rare opportunistic micro-organisms.

Background and Aim: Large number of Haemoglobin E-beta thalassaemia (Hb E/β-thalassaemia) patients show iron overloads and related end-organ damage irrespective of transfusion requirements. The prevalence of hypothyroidism in Indian population is approximately 11%. We studied the relationship between thyroid dysfunction and iron overload in Hb E/β-thalassaemia. Materials and Methods: The study included Eβ-thalassemia patients above the age of 10 years. Patient's serum ferritin level evaluated for the evaluation of iron status and thyroid-stimulating hormone, FT4, T3 for thyroid function status. Results: The study was conducted from January 2016 to December 2017. Of 50 Eβ-thalassemia patients, there were 22 females; the mean age was 19 years (range: 12–47 years). A total of 22 (44%) patients showed thyroid dysfunction; overt hypothyroidism seen in 6 (12%) patients with mean ferritin level of 1077 ng/ml and subclinical hypothyroidism seen in 16 (32%) patients with mean ferritin level of 1200 ng/ml. Normal thyroid function seen in 28 (56%) of patients with mean ferritin level of 1155 ng/ml. Conclusion: The prevalence of thyroid dysfunction was found to be higher in Hb E/β-thalassaemia patients, but a definite correlation with the serum ferritin level could not be established.

Introduction: β Haemoglobinopathy, is one of the commonest inherited disorders, with a higher prevalence in the eastern part of India. In view of the lack of facilities for allogeneic stem cell transplantation, including financial constraints, this disease is considered to be incurable in this part of India. So, preventing the birth of a symptomatic Thalassemic child is the best way to prevent the disease, considering the immense medical, social & financial implications in the community. Therefore, prenatal diagnosis is the most important tool for detecting & preventing symptomatic haemoglobinopathies. Objectives: To detect the status of haemoglobinopathies in the foetus of carrier or affected parents, so as to prevent the birth of symptomatic patients with Thalassemia & other haemoglobinopathies. Material & Methods: This is a retrospective analysis of an ongoing registry data of routine prenatal diagnosis of haemoglobinopathy, conducted at NRS Medical College, Kolkata, over a period of approximately 4 ½ years (September,2013-April,2018). The process involves, collection of Ultrasound guided chorionic villous samples (CVS) by an Obstetrician between 12-16 weeks of gestation (maximum up to 19 weeks). Considering the prevalence of specific mutations in this part of India, a total of 25 β mutations are analysed by ARMS-PCR, using specific probes. Some of the common mutations tested are: IVS1-5(G→C), 619bp del, IVS 1-1(G→T), CD 30(G→C), CD 26(G→A) & CD6 (A→T). Results: Total number of CVS were 407(407 mothers were tested), of which 329 samples (80.8%) showed presence of β haemoglobinopathy mutations, & 78(19.2%) did not have any mutations. Among the mutated genotype, heterozygous carrier state was detected in 232(57%), & homozygous/ compound heterozygous state(affected) was detected in 92 foetuses (22.6%). Among the carriers, β Thalassaemia trait was most common(n=185,45.45%), followed by HbE Trait(n=41,10.07%). HbS trait(n=3), HbD trait(n=1) & δβ Thalassemia trait (n=2) were rarely detected. Among the affected foetuses, 44 had compound heterozygous genotype (10.8%), majority being HbEβ thalassemia (n=42,10.3%), followed by δβ-β Thalassemia(n=1) & HbSβ Thalassemia(n=1). The remaining 48 affected cases were homozygous β Thalassemia Major (11.7%). Of the 92 affected pregnancies, 91(22.35%) had been counselled for medical termination of pregnancy (MTP). One case of δβ-β Thalassemia, a milder phenotype, was excluded from MTP counselling. Total number of β mutations detected (both homozygous & heterozygous states) were n=373, and the commonest was IVS1-5(G→C) (n=244,65.4%), followed by CD 26(G→A) (n=85,22.78%), CD 30(G→C) (n=9,2.4%), CD 41/42(-CTTT) (n=8,2.1%), CD 15(G→A) (n=8,2.1%) & CD8/9 (+G) (n=4,1.1%). Rarer β mutations detected were CD15(-T) (n=4,1.1%), CD16(-C) (n=1), CD6 (A→T) (n=4,1.1%), βD-PunjabCD121 (G→C) (n=3) & Asian Indian inversion deletion Gγ (Aγδβ)0(n=2). We know that sometimes maternal cell contamination may occur during villous sampling. So, at the time of childbirth, cord blood was collected & β mutation studies were re-performed. If this could not be done, an HPLC was conducted when the child was >1year old. We have data of 26 children & each time the results have corroborated with the primary CVS sampling data. Among both male and female parents(n=814), the commonest genotype was β Thalassemia Trait (n=621, 76.3%). Among the female parents(n=407), some of the other genotypes were HbE Trait (n=94,23.09%) & HbS trait(n=4,0.98%). Among the male parents(n=407), HbE Trait(n=70,17.19%) was the 2nd most common abnormality, few of the other genotypes being: HbS Trait (5,1.2%), β Thalassemia major (n=3,0.73%) & HbE homozygous disease (n=3, 0.73%). Conclusions: From this cohort, total affected (homozygous/compound heterozygous) foetuses are 92(22.6%). β Thalassemia Major (11.7%) is the most common affliction, followed by HbEβ thalassemia (10.3%) & δβ - β Thalassemia. An attempt at prevention of birth of at least 91(22.35%) future thalassemia patients has been done by means of MTP. Ours is an ongoing registry data and we are following up the children by conducting cord blood mutation studies or HPLC (>1year old child), to study the precision and accuracy of our CVS sampling results. So far there has been 100% concordance. One of the limitations of our study is lesser number of reconfirmation of the born children, in view of social and financial constraints. Disclosures No relevant conflicts of interest to declare.