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Treatment options are limited for multiple myeloma patients who have developed four/five drug-refractory disease. Selinexor (Sel) and belantamab mafodotin (belamaf) were recently approved by the US FDA for treatment of RRMM. The toxicity profile of these drugs is a concern since these agents are used in patients who have already undergone multiple lines of treatment. In this review, we discuss the toxicity profile and strategies for the management of toxicities of Sel and belamaf for the treatment of RRMM. We conducted a comprehensive literature search on PubMed, Embase, Cochrane, and Clinicaltrials.gov using the terms “selinexor”, “belantamab”, “belamaf”, and “multiple myeloma” without applying any limitations based on the date of the study, language, or country of origin. The most common hematological toxicity associated with these two drugs is thrombocytopenia. Cytopenias, constitutional symptoms, gastrointestinal effects, and hyponatremia are the major toxicities of Sel. Keratopathy and anemia are the major toxicities of belamaf. Treatment modifications and dose interruption are usually needed when side effects are more than grade II. As these are newer drugs with limited data, continuous surveillance and monitoring are warranted during the treatment course with early mitigation strategies.

Introduction Immune thrombocytopenic purpura (ITP) is an autoimmune disorder consisting of low platelet count, purpura, and hemorrhagic episodes, caused by antiplatelet autoantibodies. Children who develop chronic or refractory ITP are at risk of bleeding after failing first-line therapies. Thrombopoietin analogs -Eltrombopag and romiplostim are safe and effective treatment options. Thrombopoietin receptor agonists (TPO-Ras) improve platelet production by activating the thrombopoietin pathway. They also stimulate megakaryocytes and hematopoietic stem cells. We analyzed the efficacy and toxicity of romiplostim and eltrombopag in chronic immune thrombocytopenic purpura in the pediatric population (1-17 years). Materials/Methods Following the PRISMA guidelines, we performed a comprehensive literature search on Pubmed, Embase, Cochrane Library, Web of Science, and Clinicaltrials.gov. We used the following keywords, "Thrombopoitein analogs", "TPOs", "Immune thrombocytopenic purpura", "Eltrombopag" and "Romiplostim" MeSh terms from the inception of data till 06/17/2021. We screened initial results from the search of 358 articles focusing on the pediatric population and finally included 9 clinical trials and 1 observational study. We excluded all case reports, case series, preclinical trials, review articles, and meta-analyses. We extracted the data for efficacy (platelet response, baseline platelet count, and Platelet count at first response) and safety (Bleeding or Grade ≥ 3 Adverse Events). Results: Romiplostim A total of 185 patients were analyzed in five clinical trials and 1 observational study employing Romiplostim in the treatment group. Platelet response (PR) (platelet count >50 × 109/L) has been reported in all the studies. In 3 randomized double-blinded control trials by Bussel 2011, Elfaly 2011, and Tarantino 2016, Romiplostim achieved a platelet response of 81.69% vs 12.9% in the placebo group. The other three studies reported substantial platelet response as stated in table 1. In all the studies 25 participants had a prior splenectomy. The most common side effects reported in the studies were bleeding (56.75%), headache (58.64%), contusion (50.76%), and epistaxis (49.23%). Clinically significant bleeding (grade 2-4) was reported by 2 studies in Romiplostim vs placebo group (71.08% vs 96%). Eltrombopag A total of 246 patients were analyzed in five clinical trials and 1 observational study. In a randomized double-blinded multicenter study by Grainger et al., Eltrombopag achieved a PR of 39.68% vs 3.4% in the placebo group. Other clinical trials reported a PR of 55.85% whereas the observational study by Neuner et al. reported a PR of 72% in the patient population. Clinically significant bleeding was reported by Grainger et al. and was 47 % in the eltrombopag group vs 7% in the placebo group. Fifteen patients in all the studies had a prior splenectomy. Conclusion: Thrombopoietin analogs such as romiplostim and eltrombopag show substantial platelet response and are associated with minimal side effects. However, more randomized clinical trials are needed to compare their head-to-head efficacy and safety in the treatment of chronic immune thrombocytopenic purpura in pediatric patients. Figure 1 Figure 1. Disclosures Anwer: Janssen pharmaceutical: Honoraria, Research Funding; GlaxoSmithKline: Research Funding; Allogene Therapeutics: Research Funding; BMS / Celgene: Honoraria, Research Funding.

Introduction: Myeloproliferative neoplasms (MPN) include essential thrombocythemia (ET), polycythemia vera (PV) and primary myelofibrosis (PMF). Pregnancy in the presence of MPN increases the risk of thrombosis, hemorrhagic events, pre-eclampsia, progression to myelofibrosis (MF) or acute myeloid leukemia (AML) leading to poor fetal outcome. Methods: We conducted a literature search on PubMed, Embase, Web of Science, and Clinicaltrials.gov using MeSH terms and key words for MPN, PV, and ET from date of inception to January 2021. We excluded studies reporting less than 10 patients and those not in English language. Results: ET studies: How et al. (121 pregnancy (P)/52 women (W)) reported Aspirin (ASA) was protective and was used in 51.2% P (n=62/107) with OR (odd's ratio) of 0.304 (p=0.048; 90% CI 0.102-0.795). Similar benefit of ASA was also reported by Gangat e t al.(2009) (63P/36W ; P loss 21% in 24 patients receiving ASA vs 75% in 12 patients not receiving ASA), Niittyvuopio et al. (40P/16W; live births (LB) in all 13 P treated with ASA or ASA with prior cytoreduction therapy vs 67% complications and 56% loss of P in patients not treated with ASA), Randi et al. (1999) (16P/13W; 7/13 LB occurred on ASA, and only one P was lost on ASA), Bangerter et al.( 17P/9W; 100% P treated with ASA resulted in LB vs 45% LB in P without any treatment, p=0.04), and Pagliaro et al. (15P/9W; ASA monotherapy (n=3/15P) or ASA+ subcutaneous heparin (n=7/15P) resulted in nine LB). Cincotta e t al. (30P/12W) reported 79% LB with ASA or IFN-α vs 38% LB without any treatment (p=0.06). Among the treatment cohort, 5/7 patients on ASA had a LB, and all 4/4 patients on IFN-α had a LB. However, Beressi et al. (31P/18W) reported 4/8 untreated and 10/19 ASA treated P were lost with no statistically significant benefit. Palandri et al. reported 24P/13W treated with IFN-α (n=1), IFN-α + ASA (n=2) and ASA alone (n=9). The LB rate was not influenced significantly with treatment at conception (treated vs. untreated: 8/12 vs. 7/12, P=0.99). Melillo e t al. (122P/92W) reported no benefit with ASA. IFN-α had positive outcomes with 95% LB than patients not receiving IFN-α with 71.6% LB (OR 0.10 (95%CI: 0.013-0.846, p=0.034)). JAK2 mutation was associated with poorer outcomes (OR 6.19; 95%CI: 1.17-32.61; p=0.038). Wright et al. (43P/20W) reported no statistically significant difference between no treatment (n=16/43), ASA alone (n=24/43), ASA+cytoreduction (n=2/43), and low molecular weight heparin (LMWH) (n=1/43) groups. Passamonti et al.( 96P/58W ) reported statistically significant worse outcomes in JAK2 negative patients, no statistically significant benefit in JAK2 positive patients (p=0.05) with ASA and higher complications with conception while on cytoreduction therapy (n=6/13 abortion, n=3/13 pre-eclampsia). ET + Other MPN studies: Gangat et al. (2020) reported (152W ET and 36W PV) that in 95P/55W with ET, 60% pregnancy loss occurred without ASA vs 27% with ASA (p=0.02). All 4/36W with PV who were treated with one or more of ASA, enoxaparin, and hydroxyurea delivered LB, and 50% developed venous thromboembolism. Sokolowska et al. reported 104P/60W with MPN (47 ET, 3 PV, and 10 PMF) treated with various combinations of cytoreduction therapy (IFN-α in 48P, apheresis in 1P and anticoagulation (LMWH+ASA in 10, LMWH alone in 19 and ASA alone in 24P) during the pregnancy with 72.1% LB. Lapoirie et al. stratified 27P/14W (ET 19P/9W, PV 8P/5W) with MPN into high risk (67%) and standard risk and found significant P loss in all high-risk P that did not receive ASA (n=2). Maternal complications occurred in 3 high-risk P that received ASA. 77% of P treated with ASA, LMWH, or both resulted in a LB. Alimam et al. (58W; ET 47, PV 5, PMF 5, MPN-unclassified 1) reported better than predicted outcomes in 88% of women receiving ASA during P, 38% receiving ASA + prophylactic LMWH and 3% receiving ASA + therapeutic LMWH resulting in 58 LB with a P loss rate of 1.7/100 (95% CI; 0.04-9.24). PV studies: Irene et al. (24P/15W) reported a 40% incidence of P loss without antithrombotic therapy vs 10.5 % P loss receiving ASA, LMWH, or both. Willie e t al. divided 32P/14W with PV into two groups (treatment group: 18 P, treated with ASA during P and LMWH for six weeks postpartum; non-treatment group: 14 P) with 72% vs 14% LB respectively. Conclusion: Use of ASA, LMWH and cytoreductive therapy is the existing practice for pregnancies with MPN. However, proper evidence via a RCT is an unmet need. Figure 1 Figure 1. Disclosures Anwer: Janssen pharmaceutical: Honoraria, Research Funding; BMS / Celgene: Honoraria, Research Funding; Allogene Therapeutics: Research Funding; GlaxoSmithKline: Research Funding.

Background: Low-risk Myelodysplastic Syndromes (MDS) patients commonly present with anemia and may become blood transfusions dependent upon progression. Luspatercept, a targeted drug for an activin receptor ligand has emerged as new anemia treatment in MDS for patients with ring sideroblasts and the patients with SF3B1 mutation. This systemic review highlights the efficacy of luspatercept in MDS patients whom erythropoietin stimulating agents (ESA) are not effective. Methods: We conducted a comprehensive literature search using PubMed, Clinical trial.gov, Embase, Cochrane, and Web of science. Our search strategy included MeSH (Medical Subject Headings) terms and keywords for MDS and luspatercept including trade names and generic names from inception to 29 April 2020. Studies were selected according to PRISMA guidelines. The initial screening revealed 240 articles. After excluding review articles, duplicates, and non-relevant articles, finally we included two clinical trials, which reported transfusion independence (TI), an erythroid response (HI-E) in MDS patients with luspatercept. Proportions along with 95% Confidence Interval (CI) were extracted to compute pooled analysis using the 'meta' package by Schwarzer et al. in the R programming language (version 4.0.2) to report the efficacy of luspatercept. We pooled the results of the experimental arms of the two trials using the inverse variance method and logit transformation. Between studies, variance was calculated using DerSimonian-Laird Estimator. Results: A total of 287 patients were enrolled and evaluated in two phases II/III trials. Platzbecker et al and Fenaux et al reported Erythropoietin stimulating agents (ESA) with one median prior line of therapy (n= 148, n=46). Fenaux et al. also reported iron chelation therapy (n=71) as a prior line of therapy. Patients having ring sideroblast positive 500: n=57 for both studies. The baseline means hemoglobin (Hb) levels were eight before therapy. TI for more than eight weeks was observed in 38% of patients in both the MEDALIST trial and PACE trial. The erythroid response was 53% and 63% in both trials respectively. In a Phase II study, for LR-MDS patients, the overall erythroid response was higher among patients (n= 69%) having ringed sideroblast status (>15% ring sideroblast) and SF3B mutation (n=77%). The mean increase of Hb was observed in 29 out of 46 and 32 out of 41 pts in MEDALIST and PACE trial, respectively. Luspatercept proved to be efficacious in the pooled analysis i.e transfusion independence (TI): 38%, 95% CI 0.31-0.45; p =0.98, I2 = 0%), and erythroid response (HI-E): 54%, 95% CI 0.48-0.62; p=0.22, I2 = 32%) with an increase in mean Hb of 70% 95%: CI 0.59-0.78; I2 = 56%) (Figure 1). CONCLUSION: In patients with low risk MDS positive ringed sideroblast or SF3B1 mutation status shows good responses with luspatercept treatment, with reduced transfusion dependence, and higher erythroid response. Disclosures Anwer: Incyte Pharmaceuticals: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses, Speakers Bureau; Millennium Pharmaceuticals: Research Funding; Celgene: Research Funding; Astellas Pharma: Research Funding; Acetylon Pharmaceuticals: Research Funding; Seattle Genetics: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses, Speakers Bureau; AbbVie Pharmaceuticals: Research Funding.

Background: Conditioning regimen given before allogeneic hematopoietic stem cell transplantation (allo-HSCT) contributes significantly to the outcomes following transplant for myelodysplastic syndrome (MDS). Myeloablative conditioning (MAC) regimens are often associated with a lower risk of relapse; however, their use is often limited by toxicity and a higher risk of non-relapse mortality (NRM). Reduced-intensity conditioning (RIC) regimens are associated with a higher risk of relapse, a lower NRM, a lower incidence of graft versus host disease (GVHD), and hence is feasible in patients with advanced age or comorbidities. This study highlights the importance of the difference between the two interventions used in allo-HSCT for myelodysplastic syndrome (MDS). Methods: We conducted a comprehensive literature search using PubMed, Clinicaltrial.gov, Embase, Cochrane, and Web of Science on 5th May 2020 with no restriction of language or period. Initial research revealed 1698 articles. After excluding review articles, duplicates, and non-relevant articles, we included two randomized clinical trials and three cohort studies, which reported overall survival (OS), relapse-free survival (RFS), relapse incidence (RI), and incidence of acute and chronic (GVHD). Based on inclusion criteria, two randomized clinical trials (BMT CTN 0901 Trial Scott et al. 2017 & EBMT RICMAC Trial Kroger et al. 2017) and three cohort studies (BBMT 55226 Park et al. 2018, BBMT Orozco et al. 2019, BMT Alatrash et al. 2019) were included. Results: Among combined MDS and acute myeloid leukemia (AML) patients (n=1188) enrolled in 5 studies, 651 patients had MDS. Patients underwent MAC (n=484) or RIC (n=692) followed by either a matched related donor (MRD), n=236, or matched unrelated donor (MUD), n=236, allo-HCT. The median age range at the time of transplant was 50-54 years The use of RIC causes statistically non-significant trend of improved overall survival (OS) (OR 1.11: 95% CI: 0.74-1.67, p-value= 0.61) along with more risk of relapse incidence (RI) (R 1.34: 95% CI: 0.56-3.18, p value= 0.51), and reduced relapse free survival (RFS) (OR 0.88, 95% CI: 0.55-1.44: p value= 0.59). Differences were found in terms of safety of both conditioning regimens. MAC allo-HCT have more acute GVHD, grade 3 and 4 (OR 0.66: 95% CI: 0.29-1.52, p value= 0.33) and chronic GVHD, grade 3 and 4 (OR 0.72: 95% CI: 0.41-1.27: p value= 0.26) and treatment-related mortality (TRM) (OR 0.83, 95% CI: 0.37-1.86, p value= 0.65). The meta-analysis results are shown in figure-1. Conclusion: In adult MDS patients undergoing allo-HSCT, RIC is associated with improved overall survival, but at the cost of reduced RFS, and a higher risk of relapse. MAC, on the other hand, is associated with more treatment-related mortality and GVHD. Results of our analysis point out these trends but these are not statistically significant Figure 1 Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.: Honoraria, Research Funding, Speakers Bureau.

e20014 Background: Selinexor (Sel) and belantamab mafodotin (belamaf) were recently approved by the US FDA for treatment of relapsed/refractory multiple myeloma on July 2019 and August 2020 respectively. The toxicity profile of these drugs is a concern since these are approved for use in patients who have already undergone multiple lines of treatment. Methods: Six studies for Sel and two for belamaf were included after a systematic search of PubMed, Embase, Cochrane, and Clinicaltrials.gov. Results: The most common hematological toxicity associated with these two drugs is thrombocytopenia. The common G-3/4 hematological AEs of Sel were thrombocytopenia (39%-71%), anemia (16%-33%), leukopenia (8%-33%) and neutropenia (9%-33%) whereas common G-3/4 non-hematological AEs were hyponatremia (5%-26%), fatigue (13%-15%), diarrhea (5%-10%), eye disorders (9%-10%), musculoskeletal disorders (4%-10%), elevated liver enzymes (10%), peripheral neuropathy (5%) and vomiting (2-4%). Keratopathy and anemia were the major toxicities of belamaf. Most of these toxicities are manageable. Treatment modifications and dose interruption are usually needed when AEs are more than grade II. REMS program guidelines is recommended for close monitoring and evaluation of Sel and belamaf toxicities and early ophthalmological intervention. Conclusions: As these are newer drugs with limited data, continuous surveillance and monitoring is warranted during the treatment course with early mitigation strategies. The physician should be aware of thrombocytopenia and its management as well as belamaf ocular toxicity which is manageable but if missed could have serious complications.[Table: see text]