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Background Optimal cytoreduction to no residual disease (R0) correlates with improved disease outcome for high-grade serous ovarian cancer (HGSOC) patients. Treatment of HGSOC patients with neoadjuvant chemotherapy, however, may select for tumor cells harboring alterations in hallmark cancer pathways including metastatic potential. This study assessed this hypothesis by performing proteomic analysis of matched, chemotherapy naïve and neoadjuvant chemotherapy (NACT)-treated HGSOC tumors obtained from patients who had suboptimal (R1, n = 6) versus optimal (R0, n = 14) debulking at interval debulking surgery (IDS). Methods Tumor epithelium was harvested by laser microdissection from formalin-fixed, paraffin-embedded tissues from matched, pre- and post-NACT treated tumors for twenty HGSOC patients and analyzed by quantitative mass spectrometry-based proteomics. Results Differential analysis of patient matched pre- and post-NACT treated tumors revealed proteins associated with cell survival and metabolic signaling to be significantly altered in post-NACT treated tumor cells. Comparison of pre-NACT treated tumors from suboptimal (R1) versus optimally (R0) debulked patients identified proteins associated with tumor cell viability and invasion signaling enriched in R1 patients. We identified five proteins altered between R1 and R0 patients in pre- NACT treated tumors that significantly correlated with PFS in an independent cohort of HGSOC patients, including Fermitin family homolog 2 (FERMT2), a protein elevated in R1 that correlated with disease progression in HGSOC patients (multivariate Cox HR = 1.65, Wald p = 0.022) and increased metastatic potential in solid-tumor malignancies. Conclusions This study identified distinct proteome profiles in patient matched pre- and post-NACT HGSOC tumors that correlate with NACT resistance and that may predict residual disease status at IDS that collectively warrant further pre-clinical investigation.

Measurable residual disease (MRD) evaluation may help to guide treatment duration in multiple myeloma (MM). Paradoxically, limited longitudinal data exist on MRD during maintenance. We investigated the prognostic value of MRD dynamics in 1280 transplant-eligible and -ineligible patients from the TOURMALINE-MM3 and -MM4 randomized, placebo-controlled, phase 3 studies of 2-year ixazomib maintenance. MRD status at randomization showed independent prognostic value (median progression-free survival [PFS]: 38.6 vs 15.6 months in MRD- vs MRD+ patients, HR 0.47). However, MRD dynamics during maintenance provided more detailed risk stratification. A 14-month landmark analysis showed prolonged PFS in patients converting from MRD+ to MRD- status vs those with persistent MRD+ status (76.8% vs 27.6% 2-year PFS rates). Prolonged PFS was observed in patients with sustained MRD- status vs those converting from MRD- to MRD+ status (75.0% vs 34.2% 2-year PFS rates). Similar results were observed at a 28-month landmark analysis. Ixazomib maintenance vs placebo improved PFS in patients who were MRD+ at randomization (median 18.8 vs 11.6 months, HR 0.65) or at the 14-month landmark (median 16.8 vs 10.6 months, HR 0.65); no difference was observed in patients who were MRD-. This is the largest MM population undergoing yearly MRD evaluation during maintenance reported to date. We demonstrate the limited prognostic value of a single timepoint MRD evaluation, because MRD dynamics over time substantially impact PFS risk. These findings support MRD- status as a relevant endpoint during maintenance and confirm the increased progression risk in patients converting to MRD+ from MRD- status.

Cytogenetic abnormalities (CA) such as t(4;14), t(14;16), and del(17p), are associated with a poor prognosis in Multiple Myeloma (MM) patients. However, there is scarce information regarding the Latin-American population. This study aims to analyze the impact of t(4;14), t(14;16), and del(17p) on the progression-free survival (PFS) and overall survival (OS) of transplant-eligible newly-diagnosed MM (NDMM) patients in Latin America. Retrospective survival analysis based on the Grupo de Estudio Latinoamericano de MM (GELAMM) registry, including all adult patients with NDMM harboring CA t(4;14), t(14;16), and/or del(17p). Fifty-nine patients were included; the median age was 57 years, 55.9% males, 22% ISS-I, 25.4% ISS-II, and 47.5% ISS-III. The majority (89.8%) had 1 alteration, whereas 10.2% had del(17p) and t(4;14). The frequencies of CA were del(17p) in 61.0%, t(4;14) in 25.4%, and t(14;16) in 3,4%. Autologous stem cell transplantation (ASCT) was performed in 61.0% of cases. Five-year OS for the entire cohort was 60.8% and 5-year PFS was 28.1%. Bortezomib-based induction regimen (BBR) (P = 0.029), consolidation with ASCT (P0.001), and maintenance therapy (P = 0.004) were associated with an improved 5-year OS. In the multivariate analysis, ASCT was the only variable with a positive impact on OS (HR 0.11, 95% CI 0.033 to 0.34, P0.001). The median PFS presented a non-statistically significant benefit in BBR, ASCT, and maintenance therapy groups. BBR induction, ASCT, and maintenance therapy were associated with improved OS in high-risk NDMM patients.

The tumor microenvironment (TME) represents a complex ecosystem comprised of dozens of distinct cell types, including tumor, stroma, and immune cell populations. To characterize proteome-level variation and tumor heterogeneity at scale, high-throughput methods are needed to selectively isolate discrete cellular populations in solid tumor malignancies. This protocol describes a high-throughput workflow, enabled by artificial intelligence (AI), that segments images of hematoxylin and eosin (HE)-stained, thin tissue sections into pathology-confirmed regions of interest for selective harvest of histology-resolved cell populations using laser microdissection (LMD). This strategy includes a novel algorithm enabling the transfer of regions denoting cell populations of interest, annotated using digital image software, directly to laser microscopes, thus enabling more facile collections. Successful implementation of this workflow was performed, demonstrating the utility of this harmonized method to selectively harvest tumor cell populations from the TME for quantitative, multiplexed proteomic analysis by high-resolution mass spectrometry. This strategy fully integrates with routine histopathology review, leveraging digital image analysis to support enrichment of cellular populations of interest and is fully generalizable, enabling harmonized harvests of cell populations from the TME for multiomic analyses.

The aim of this study was to describe clinical and survival characteristics of transplant-eligible multiple myeloma (MM) patients in Latin America (LA), with a special focus on differences between public and private healthcare facilities. We included 1293 patients diagnosed between 2010 and 2018. A great disparity in outcomes and survival between both groups was observed. Late diagnosis and low access to adequate frontline therapy and ASCT in public institutions probably explain these differences. Patients treated with novel drug induction protocols, followed by autologous stem cell transplantation (ASCT) and maintenance, have similar overall survival compared to that published internationally.

Measurable residual disease (MRD) evaluation may help to guide treatment duration in multiple myeloma (MM). Paradoxically, limited longitudinal data exist on MRD during maintenance. We investigated the prognostic value of MRD dynamics in 1280 transplant-eligible and -ineligible patients from the TOURMALINE-MM3 and -MM4 randomized placebo-controlled phase 3 studies of 2-year ixazomib maintenance. MRD status at randomization showed independent prognostic value (median progression-free survival [PFS], 38.6 vs 15.6 months in MRD− vs MRD+ patients; HR, 0.47). However, MRD dynamics during maintenance provided more detailed risk stratification. A 14-month landmark analysis showed prolonged PFS in patients converting from MRD+ to MRD− status vs those with persistent MRD+ status (76.8% vs 27.6% 2-year PFS rates). Prolonged PFS was observed in patients with sustained MRD− status vs those converting from MRD− to MRD+ status (75.0% vs 34.2% 2-year PFS rates). Similar results were observed at a 28-month landmark analysis. Ixazomib maintenance vs placebo improved PFS in patients who were MRD+ at randomization (median, 18.8 vs 11.6 months; HR, 0.65) or at the 14-month landmark (median, 16.8 vs 10.6 months; HR, 0.65); no difference was observed in patients who were MRD−. This is the largest MM population undergoing yearly MRD evaluation during maintenance reported to date. We demonstrate the limited prognostic value of a single–time point MRD evaluation, because MRD dynamics over time substantially impact PFS risk. These findings support MRD− status as a relevant end point during maintenance and confirm the increased progression risk in patients converting to MRD+ from MRD− status. These trials were registered at www.clinicaltrials.gov as #NCT02181413 and #NCT02312258.

Background Monoclonal gammopathy of renal significance (MGRS)-related lesions are infrequent entities. There are no publications on these disorders in Latin America (LA). The aim of this study was to describe epidemiological and clinical characteristics of these patients in LA. Methods We performed a multicentre retrospective study. Patients with diagnosis of MGRS between 2012 and 2018 were included. Epidemiological and clinical data were collected from clinical records. Results Twenty-seven patients from Chile, Argentina, Ecuador and Uruguay were included. Half debuted with a nephrotic syndrome, and 32% required dialysis. Proliferative glomerulonephritis with monoclonal immunoglobulin deposits was found in 33%, amyloidosis in 26% and monoclonal immunoglobulin deposition disease also in 26%. The immunoglobulin most frequently found in renal biopsies was IgG kappa. In 67% a paraprotein was found. Twenty patients received an anti-plasma cell regimen, and 3 a rituximab-based regimen (IgM-MGRS). Renal response (RR) was achieved in 56%. Early treatment (≤3 months) was associated with higher RR (75% vs 43%). Three patients relapsed within 21.5 months, and 3 progressed: 1 to multiple myeloma, 1 to systemic amyloidosis and another to systemic light-chain deposition disease. Two patients died, both due to infection during induction treatment. Conclusion There was a higher than expected frequency of patients requiring dialysis. The most common MGRS-related lesion was PGNMD. Early treatment was associated with better response. As a rare disease, increasing awareness and promoting early diagnosis are necessary in LA to improve outcomes. SUMMARY AT A GLANCE A collection of 27 cases of MGRS from Latin America with information on epidemiology, clinical characteristics, treatment and outcome of patients diagnosed of MGRS-related renal lesions.

Aplastic anemia (AA) is a rare but serious disease that affects hematopoietic stem cells and is characterized by pancytopenia and a hypocellular bone marrow. It can be a hereditary or acquired condition. Acquired AA has an incidence of 2 per million per year in Europe, but the incidence is two to three times higher in Asia. In Latin America, there is little epidemiologic data on this disease. The most important treatments for AA are bone marrow transplantation and immunosuppressive treatment with antithymocyte globulin and cyclosporine. But access to these treatments is restricted in some areas of Latin America. At the American Society of Hematology (ASH) Annual Meeting in 2016, representatives of the Hematology Societies of Latin America, with the support of the ASH International Program, met to discuss possible collaborative efforts. Everyone agreed that lack of reliable information is one of the main barriers to designing significant clinical trials for the region; therefore, starting a registry of hematologic diseases for the region has become a main goal of the group. In April 2017, at the ASH Highlights meeting in Latin America, AA was selected as the first disease that would be used to begin the collaborative action. National hematology societies of Argentina, Bolivia, Brazil, Chile, Colombia, Costa Rica, Paraguay, Peru, Uruguay, and Venezuela have made a commitment to help develop the Latin American Registry for Aplastic Anemia (LARAA).

Background The treatment of choice of newly diagnosed multiple myeloma (NDMM) is an induction with proteasome inhibitors followed autologous stem cell transplantation (HSCT). Since 2013, the treatment of these patients in the public system is based on CTD (cyclophosphamide, thalidomide, and dexamethasone). Aim To evaluate the response rates achieved with CTD, and the results of HSCT in patients with NDMM in the public setting. Material and Methods Data from patients considered as candidates for HSCT from different centers of the National Adult Antineoplastic Drug Program (PANDA, for its acronym in Spanish), diagnosed between 2013 and 2017, was analyzed. The response to treatment of first and second lines of treatment was evaluated, in addition to the results of HSCT. An optimal Response was defined as the sum of strict complete remission, complete remission and very good partial response (sCR, CR and VGPR). Results One hundred and seventy-seven patients were analyzed, 54% women, and 53% with IgG multiple myeloma. Information about the international staging system was retrieved in 127 patients (71%). Seventeen percent were ISS I, 22% in ISS II and 32% ISS III. CTD was used as first treatment in 106 patients (60%), and cyclophosphamide, bortezomib and dexamethasone (CyBorD) in 13 (7%). As first line, CTD had an overall response of 50.9%, and CyBorD of 76.9%. Thirty patients were treated with bortezomib as second line treatment. Forty patients (22%) underwent HSCT. The 5-year Overall Survival (OS) in transplanted patients and non-transplanted patients was 100 and 62% respectively (p < 0.01). Conclusions The response rate achieved by CTD in these patients is suboptimal. The response to CyBorD was better.

Summary Enriched tumor epithelium, tumor-associated stroma, and whole tissue were collected by laser microdissection from thin sections across spatially separated levels of ten high-grade serous ovarian carcinomas (HGSOCs) and analyzed by mass spectrometry, reverse phase protein arrays, and RNA sequencing. Unsupervised analyses of protein abundance data revealed independent clustering of an enriched stroma and enriched tumor epithelium, with whole tumor tissue clustering driven by overall tumor “purity.” Comparing these data to previously defined prognostic HGSOC molecular subtypes revealed protein and transcript expression from tumor epithelium correlated with the differentiated subtype, whereas stromal proteins (and transcripts) correlated with the mesenchymal subtype. Protein and transcript abundance in the tumor epithelium and stroma exhibited decreased correlation in samples collected just hundreds of microns apart. These data reveal substantial tumor microenvironment protein heterogeneity that directly bears on prognostic signatures, biomarker discovery, and cancer pathophysiology and underscore the need to enrich cellular subpopulations for expression profiling., Graphical abstract, Highlights • LMD was used to investigate 3-D molecular heterogeneity in ovarian cancer tissue • Diverse molecular profiles were identified from 3-D spatially separated samples • Molecular heterogeneity impacts HGSOC prognostic sub-type assignment • Proteomic heterogeneity analysis web portal deployed at www.lmdomics.org, Oncology; Cancer systems biology; Proteomics; Transcriptomics

Background The SARS CoV-2 / COVID 19 pandemic has challenged the world's health systems, especially services that treat cancer. The first studies in China showed that cancer patients had a higher risk of becoming infected and dying. Other risk factors for mortality were age over 65 years, male sex, the presence of comorbidity, hypertension, cardiovascular disease, diabetes, and obesity. Data on the specific behavior of patients with multiple myeloma (MM) in the pandemic are scarce. The mechanisms by which MM patients may have a higher mortality are multiple, derived both from the disease itself due to cellular and humoral immunity deficiency as well as from anti-myeloma treatment. The present study aims to establish the behavior of the disease in the pandemic period in Latin America. Methods This is a retrospective case series of in and outpatients with a diagnosis of MM and COVID-19 reported from centers from Latin America between March and July 31, 2020. The analysis of demographic, clinical, laboratory, complications and therapy variables were done using descriptive statistics. A Kaplan Meier survival analysis was performed, with Log Rank statistic. Finally, a Cox regression was performed to identify independent risk factors of worse outcome. Pre-admission characteristics, MM status, and comorbidities constituted the reference model and were used to adjust the association of relevant MM characteristics with mortality. Program used for analysis was SPSS statistics 25. Results Fifty-two patients with COVID-19 and MM from 7 countries were included. Demographic characteristics, comorbidities, infection baseline clinical conditions, treatment, and outcomes are shown in Table 1. The characteristics in terms of MM status are shown in Table 2. When performing the survival analysis, it is evidenced that the survival of the entire cohort at day 49 was 67% Figure 1. When we focus on patients with comorbidities, survival drops to 53.5% +/- 10.6 (CI 95% 53.4 - 99.4 and p value of 0.041) for the same day Figure 2. When performing the obesity analysis, a drop in survival of up to 39% was observed (95% CI 24.448 - 56.76, with p = 0.00001) Figure 3. Adjusted HR for obesity is 5,078 (95% CI 1,389-18,558, α0.014) and mechanical ventilation with a HR of 3,943 (95% CI - 1,296 - 11,998, α0.016) When comparing patients with controlled MM (> PR) versus uncontrolled, the mortality rate was 84% versus 58% respectively (p = 0.109). Comorbidities (presence of either diabetes, arterial hypertension, cardiovascular disease, or "others"), obesity, need of mechanical ventilation, and Conclusions Patients with MM and COVID-19 has an overall mortality of approximately 30% and this is strongly influenced by the presence of comorbidities, uncontrolled disease and need of mechanical ventilation. Survival of patients without comorbidities and controlled disease is good, suggesting that this group of patients would not require modification of MM therapy. The main limitations of our study are its retrospective nature and the low number of patients. It must be highlighted that at the time of the analysis most of Latin American countries were still in the peak of the pandemic. Prospective studies are required to elucidate the behavior of these risk factors in mortality, to optimize the management of patients with MM in this period of the SARS CoV-2 / COVID-19 pandemic. Disclosures Peña: BindingSite: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sandoz: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Amgen: Speakers Bureau. Abello:Novartis: Consultancy, Honoraria; Amgen: Consultancy, Research Funding; Takeda: Honoraria, Research Funding; Dr. Reddy's: Consultancy, Research Funding; Abbvie: Consultancy, Research Funding. Idrobo:Abbvie: Honoraria, Speakers Bureau; Tecnofarma: Honoraria, Speakers Bureau; Takeda: Honoraria, Speakers Bureau; Janssen: Honoraria, Speakers Bureau; Amgen: Honoraria, Speakers Bureau. Rojas:Novartis: Consultancy; Roche: Honoraria; Sandoz: Honoraria; Abbvie: Honoraria. Remaggi:Takeda: Honoraria; Raffo Argentina: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Gador Argentina: Research Funding; Amgen: Honoraria, Research Funding. Alvarado:Celgene: Speakers Bureau; Alexion: Speakers Bureau; Amgen: Speakers Bureau; Novartis: Speakers Bureau; Roche: Speakers Bureau. De la Peña-Celaya:Amgen: Speakers Bureau; Janssen: Speakers Bureau; Novartis: Speakers Bureau. Perez:Novartis: Speakers Bureau; Celgene: Speakers Bureau; Roche: Speakers Bureau.

As the understanding of cancer biology expands, a wider array of treatment options has become available in the field of gynecologic cancer. Therapies that target specific molecular pathways are now being used. Drugs that target cancer angiogenesis, signal transduction, DNA repair, and immune evasion mechanisms are currently being used, in addition to or in lieu of traditional chemotherapy, to achieve more personalized treatment of each patient and their unique disease. These therapies may lead to improved survival outcomes and quality of life during treatment and during remission.

Philadelphia-negative myeloproliferative neoplasms (Ph-MPN) are chronic hematological disorders characterized by the overproduction of one or more mature myeloid blood cell lineages. Classical Ph-MPN are polycythemia vera (PV), essential thrombocytopenia (ET) and primary myelofibrosis (PMF).To assess the epidemiological, clinical and diagnostic characteristics of Ph-MPN in Chile.Retrospective review of medical records of all patients referred as MPN from 2012 to 2017. Patients with (9;21) translocation were excluded.Data of 462 cases with a median age of 69 years from 10 public hospitals was reviewed. ET was the most frequently Ph-MNP found. The incidence of Ph-MPN was 1.5 x 100.000 cases. The JAK2 V617F mutation study was performed in 96% of patients and only 30% had a bone marrow biopsy. Thrombotic events were observed in 29% of patients. Bleeding events were observed in 7%. Five-year overall survival was 87%.ET is the most frequent Ph-MPN. The mean incidence was lower than reported in the literature, in part because of a sub diagnosis.

In PACE (Ponatinib Ph+ ALL and CML Evaluation), a phase 2 trial of ponatinib that included patients with chronic-phase chronic myeloid leukemia (CP-CML) resistant to multiple prior tyrosine kinase inhibitors (TKIs), ponatinib showed deep and durable responses, but arterial occlusive events (AOEs) emerged as notable adverse events. Post hoc analyses indicated that AOEs are dose dependent. We assessed the benefit/risk ratio across 3 ponatinib starting doses in the first prospective study to evaluate a novel, response-based, dose-reduction strategy for TKI treatment. Adults with CP-CML resistant to or intolerant of at least 2 prior BCR-ABL1 TKIs or with a BCR-ABL1 T315I mutation were randomly assigned 1:1:1 to 3 cohorts receiving ponatinib 45, 30, or 15 mg once daily. In patients who received 45 or 30 mg daily the dose was reduced to 15 mg upon response (BCR-ABL1IS transcript levels ≤1%). The primary end point was response at 12 months. From August 2015 through May 2019, 283 patients were randomly assigned to the cohorts: 282 (94 per dose group) received treatment (data cutoff, 31 May 2020). The primary end point (98.3% confidence interval) was achieved in 44.1% (31.7-57.0) in the 45-mg cohort, 29.0% (18.4-41.6) in the 30-mg cohort, and 23.1% (13.4-35.3) in the 15-mg cohort. Independently confirmed grade 3 or above treatment-emergent AOEs occurred in 5, 5, and 3 patients in the 45-, 30-, and 15-mg cohorts, respectively. All cohorts showed benefit in this highly resistant CP-CML population. Optimal benefit/risk outcomes occurred with the 45-mg starting dose, which was decreased to 15 mg upon achievement of a response. This trial is registered on www.clinicaltrials.gov as NCT02467270.

Introduction: SARS-COV-2 pandemic has infected approximately 20 million people worldwide and more than 700.000 fatalities have been reported. Patients with malignant hematological diseases are at particular risk for unfavorable outcomes, including intensive care unit (ICU) admission, need for mechanical ventilation (MV) and death. There is paucity of data of the outcome of cancer patients with COVID-19 in low- and middle-income countries. GELL is a collaborative network of hematological centers in 13 countries in Latin America. In this retrospective study, we aimed to look at the outcome of lymphoma patients diagnosed with COVID-19 in Latin America. Methods: This is a retrospective study including patients with a diagnosis of lymphoma and COVID-19 infection. Patients with chronic lymphocytic leukemia/small lymphocytic lymphoma were excluded from the analysis. COVID-19 diagnosis was done by RT-PCR in all but 3 patients, in whom the diagnosis was done by serology. Active disease was defined as patients with detected disease in any setting (prior to therapy, relapse) or patients currently on treatment. Survival curves were plotted using Kaplan Meier method. Results: A total of 117 patients were available for analysis. Median age was 60 years old, and 44% of patients had at least one comorbidity, including 32% with hypertension, 17% with obesity, 11% with cardiovascular disease and 17% with diabetes. Most patients had aggressive lymphomas (67%), including 46% of patients with diffuse large B-Cell lymphoma (DLBCL). Follicular lymphomas was observed in 13% of patients and Hodgkin's lymphoma in 10% of patients. 84% of patients had active disease, and 70% of patients were currently on treatment. With a median follow up of 17 days from COVID-19 diagnosis, 78% were admitted to Hospital, 30% needed ICU support, and 27% needed MV. Importantly, 26% of patients died, most of them within 20 days from diagnosis (Fig. 1). There was no relation between active disease (p=0.23), current treatment (p=0.65) or use of monoclonal antibodies (p=0.24) with death. COVID-19 treatment data was available in 107 patients, and 72 of them received any treatment, being steroids, the most common treatment used (n=59). Conclusion: We confirm the dismal prognosis of patients with hematological malignancies and COVID-19 infection. In our cohort of Latin America patients with lymphoma and COVID-19, 26% of patients died with a median follow up of 17 days. No impact of current treatment or use of monoclonal antibodies were observed. Figure Disclosures Peña: Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sandoz: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Amgen: Speakers Bureau; BindingSite: Research Funding. Idrobo:Amgen: Honoraria, Speakers Bureau; Abbvie: Honoraria, Speakers Bureau; Janssen: Honoraria, Speakers Bureau; Tecnofarma: Honoraria, Speakers Bureau; Takeda: Honoraria, Speakers Bureau. Abello:Novartis: Consultancy, Honoraria; Amgen: Consultancy, Research Funding; Takeda: Honoraria, Research Funding; Dr. Reddy's: Consultancy, Research Funding; Abbvie: Consultancy, Research Funding. Rojas:Novartis: Consultancy; Abbvie: Honoraria; Sandoz: Honoraria; Roche: Honoraria. Castillo:Beigene: Consultancy, Research Funding; Abbvie: Research Funding; Pharmacyclics: Consultancy, Research Funding; TG Therapeutics: Research Funding; Kymera: Consultancy; Janssen: Consultancy, Research Funding. Villela:amgen: Speakers Bureau; Roche: Other: advisory board, Speakers Bureau.

En diciembre de 2019 se detectó por primera vez en China la existencia del SARS-CoV2, causante de la enfermedad COVID-19. El virus rápidamente se propagó por Europa y Asia, tardándose un par de meses antes de llegar a América Latina. Se ha demostrado que los pacientes que desarrollan una enfermedad severa y que tienen mayor riesgo de mortalidad por COVID-19 son aquellos con edades avanzadas y que presentan por lo menos una enfermedad crónica, incluyendo el cáncer. Debido a lo anterior, surgen muchas dudas en el grupo de profesionales encargados de brindar tratamiento a pacientes con cáncer durante la pandemia, pues se debe equilibrar el riesgo-beneficio de proveer tratamiento a pacientes que se encuentran de base con un riesgo incrementado para tener manifestaciones severas por COVID-19. En este consenso planteamos recomendaciones para los profesionales en hematología que brindan tratamiento a pacientes que padecen de algún tipo de linfoma, con el fin de aclarar el panorama clínico durante la pandemia.

Isolated splenic metastases are rare in gynecologic cancer but may occur due to recurrent uterine or ovarian cancer.[1][1] Our objective in this video is to demonstrate the feasibility of robotic-assisted splenectomy for recurrent gynecologic cancer. We examined a case of isolated splenic metastasis

Updated analysis confirms sustained poor prognosis of COVID-19 in patients with lymphoma in Latin America: A cohort of 160 patients from GELL. Introduction: Ongoing SARS-COV-2 pandemic has impacted the management of cancer patients worldwide. Several reports have demonstrated inferior outcomes of patients with hematological malignancies, including higher rates of intensive care unit admission, need for mechanical ventilation and death. The impact of COVID-19 is profound in resource-restricted countries, including Latin America. Most cohorts reported have not included patients from Latin America, and there is paucity of data of the outcome of cancer patients with COVID-19 in low- and middle-income countries. Grupo de Estudio De Linfoproliferativos En Latino-America (GELL )is a collaborative network of hematological centers in 13 countries in Latin America. We report updated outcomes of lymphoma patients diagnosed with COVID-19 in Latin America. Methods: We conducted a retrospective study including patients with a diagnosis of lymphoma and COVID-19 infection. Patients with chronic lymphocytic leukemia/small lymphocytic lymphoma were excluded from the analysis We defined active disease as follow: (1) patients with detectable disease either prior to initiating therapy or upon relapse, and/or (2) patients undergoing active cancer treatment. The primary outcome was overall survival at 100 days. Survival curves were estimated using the Kaplan Meier method. Uni and multivariable analysis were carried out with Cox model. Results: A total of 160 patients were available for analysis. Median age was 60 years old. Hypertension was the most common comorbidity (33%). Most patients had aggressive lymphomas (62%), including 43% of patients with diffuse large B-Cell lymphoma (DLBCL). Follicular lymphomas were observed in 13% of patients and Hodgkin lymphoma in 12.5% of patients. With a median follow-up of 37 days, the 100-day OS was 64% (95CI 56-74%, fig. 1). In univariate analysis, age (HR 1.03, p=0.0025), hypertension (HR 2.01, p=0.017), >1 number of prior lines (HR 2.78, p=0.011), patients currently on treatment (HR 1.83, p=0.043), ferritin >2000 ng/mL (HR 4.74 p=0.00047) were associated with inferior OS. In multivariate analysis, age (HR 1.03, p=0.0026) and patients currently on treatment (HR 1.82, p=0.04) had inferior OS. There was a trend towards inferior outcomes in patients receiving monoclonal antibodies in univariate analysis (HR 1.82, p=0.081) but not in multivariable analysis (HR=1.29, p=0.48). Use of steroids was not statistically related to mortality (HR 1.79, p=0.074). Finally, contrary to other cohorts, no improvement in OS was observed in patients diagnosed later on the pandemic (fig. 2). Conclusion: In this large cohort of Latin American patients with lymphoma malignancies, our updated analysis showed a maintained dismal prognosis with COVID-19 infection. With a median follow up of 37 days, the 100-day OS was 64%. Older age and ongoing active cancer treatment were significantly associated with mortality. The use of monoclonal antibodies and systemic corticosteroids were not statistically associated to poor survival. Current efforts are focused on improving immunization in the Latin American population. There is an unmet need for improving survival in patients with hematologic malignancies and COVID-19 infection. Figure 1 Figure 1. Disclosures Perini: Janssen: Honoraria, Speakers Bureau; Takeda: Honoraria, Speakers Bureau; Astra Zeneca: Honoraria, Speakers Bureau; MSD: Honoraria, Speakers Bureau. Otero: ASTRA ZENECA: Current Employment. Abello: Dr Reddy's: Research Funding; Amgen: Honoraria; Janssen: Honoraria. Castillo: Abbvie: Consultancy, Research Funding; BeiGene: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; Janssen: Consultancy; Roche: Consultancy; TG Therapeutics: Research Funding.

Background: Immunoglobulin light chain (AL) amyloidosis is a rare and underdiagnosed entity. Aim: To characterize patients with AL amyloidosis in Chilean public health centers. Material and Methods: We conducted a retrospective, multicenter study. Public centers of the Chilean Monoclonal Gammopathies Cooperative Group were asked to search for patients with AL amyloidosis in their databases. Epidemiological, clinical and laboratory characteristics were evaluated. Results: Forty-two patients aged 22 to 84 years were found. Twenty four percent had localized AL amyloidosis; 64% had a lambda light chain clone; 47% were associated with multiple myeloma and 9% with non-Hodgkin lymphoma. The most commonly involved organ was the kidney (76%). Serum free light chains were measured in 31% and an echocardiogram was performed in 74% of patients. Seventeen percent of patients received only palliative care, 17% were treated with bortezomib, 21% with thalidomide, and 40% with melphalan. No patient was transplanted. The mean overall survival (OS) of the group was 19 months. The 5-year OS was 28%. Conclusions: It is important to obtain these realistic, national data to initiate strategies to improve early diagnosis and proper management of this disease.

To investigate racial disparities in uterine carcinosarcoma (UCS) and ovarian carcinosarcoma (OCS) in Commission on Cancer®-accredited facilities.Non-Hispanic Black (NHB) and non-Hispanic White (NHW) women in the National Cancer Database diagnosed with stage I-IV UCS or OCS between 2004 and 2014 were eligible. Differences by disease site or race were compared using Chi-square test and multivariate Cox analysis.There were 2830 NHBs and 7366 NHWs with UCS, and 280 NHBs and 2586 NHWs with OCS. Diagnosis of UCS was more common in NHBs (11.5%) vs. NHWs (3.7%) and increased with age (P .0001). OCS diagnosis remained5% in both races and all ages. NHBs with UCS or OCS were more common in the South and more likely to have a comorbidity score ≥ 1, low neighborhood income and Medicaid or no insurance (P .0001). Diagnosis at stage II-IV was more common in NHBs than NHWs with UCS but not OCS. NHBs with both UCS and OCS were less likely to undergo surgery and to achieve no gross residual disease with surgery (P = .002). Risk of death in NHB vs. NHW patients with UCS was 1.38 after adjustment for demographic factors and dropped after sequential adjustment for comorbidity score, neighborhood income, insurance status, stage and treatment by 4%, 16%, 7%, 19% and 10%, respectively, leaving 43.5% of the racial disparity in survival unexplained. In contrast, risk of death in NHBs vs. NHWs with OCS was 1.19 after adjustment for demographic factors and became insignificant after adjustment for comorbidity. Race was an independent prognostic factor in UCS but not in OCS.Racial disparities exist in characteristics, treatment and survival in UCS and OCS with distinctions that merit additional research.

Background The treatment of choice of newly diagnosed multiple myeloma (NDMM) is an induction with proteasome inhibitors followed autologous stem cell transplantation (HSCT). Since 2013, the treatment of these patients in the public system is based on CTD (cyclophosphamide, thalidomide, and dexamethasone). Aim To evaluate the response rates achieved with CTD, and the results of HSCT in patients with NDMM in the public setting. Material and Methods Data from patients considered as candidates for HSCT from different centers of the National Adult Antineoplastic Drug Program (PANDA, for its acronym in Spanish), diagnosed between 2013 and 2017, was analyzed. The response to treatment of first and second lines of treatment was evaluated, in addition to the results of HSCT. An optimal Response was defined as the sum of strict complete remission, complete remission and very good partial response (sCR, CR and VGPR). Results One hundred and seventy-seven patients were analyzed, 54% women, and 53% with IgG multiple myeloma. Information about the international staging system was retrieved in 127 patients (71%). Seventeen percent were ISS I, 22% in ISS II and 32% ISS III. CTD was used as first treatment in 106 patients (60%), and cyclophosphamide, bortezomib and dexamethasone (CyBorD) in 13 (7%). As first line, CTD had an overall response of 50.9%, and CyBorD of 76.9%. Thirty patients were treated with bortezomib as second line treatment. Forty patients (22%) underwent HSCT. The 5-year Overall Survival (OS) in transplanted patients and non-transplanted patients was 100 and 62% respectively (p0.01). Conclusions The response rate achieved by CTD in these patients is suboptimal. The response to CyBorD was better.

Objectives In PACE ( NCT01207440 ), heavily pretreated patients with chronic-phase chronic myeloid leukemia (CP-CML) demonstrated deep, lasting ponatinib responses; long-term follow-up showed increasing rates of arterial occlusive events (AOEs). We present OPTIC ( NCT02467270 ) interim analysis (IA) results, evaluating the association between ponatinib exposure, efficacy, and safety. Methods This phase 2 trial randomized patients with CP-CML resistant/intolerant to ≥2 tyrosine kinase inhibitors (TKIs) or with a T315I mutation to ponatinib starting doses of 45 mg (cohort A), 30 mg (B), and 15 mg (C) qd. Doses were reduced to 15 mg qd on achievement of ≤1% BCR-ABL1IS in A/B. Primary endpoint: 12-month ≤1% BCR-ABL1IS; secondary endpoints include cytogenetic and molecular response, and AOE, venous thromboembolism (VTE), and treatment-emergent adverse event rates. IA results are descriptive and will be inferential by adjusting multiplicity across 3 cohorts at final analysis. Results 283 patients were randomized (A/B/C: n=94/95/94); median age 48 y (range, 18-81 y). 26% had hypertension history; 2/43/55% received 1/2/ ≥3 TKIs; 40% had ≥1 baseline mutations, with 23% T315I, all well balanced between cohorts. At IA data cutoff (20 Jul 2019), 162 patients (57%; n=57/51/54) remained on treatment. Within the safety population (N=282), median duration of exposure was ∼1 y (A/B/C, 14/12/12 mo). At 12 mo, 39% (95% CI, 27.6, 50.6), 27% (17.6, 39.1), and 26% (16.5, 38.6) in A, B, and C, respectively, achieved ≤1% BCR-ABL1IS. Dose reductions due to efficacy (A/B): 35/21%. Molecular responses were maintained in all patients who were on the reduced dose for at least 90 days (n=37). Most common TEAEs (any grade/≥3): thrombocytopenia 39/27%, neutropenia 25/17%. AOEs/serious AOEs were reported by (A, B, C) in 5%/2%, 4%/3%, and 1%/0%. Dose reductions for TEAEs: (A/B/C): 44/31/28%; discontinuations due to TEAEs: 18/15/14%. There were 4 (1.4%) on-study deaths; A, sudden death, n=2; C, pneumonia, n=2; no deaths were due to AOEs. Conclusions OPTIC IA shows a trend toward dose-dependent efficacy and safety, and may provide a refined understanding of the ponatinib benefit:risk profile and its relation to dose. Data from longer follow-up may support an alternate dosing regimen for patients with CP-CML.

7502 Background: In PACE (NCT01207440) heavily pretreated patients (pts) with chronic-phase CML (CP-CML) had deep, lasting responses to PON; long-term follow-up showed increasing rates of arterial occlusive events (AOEs). We present IA results from OPTIC (NCT02467270), evaluating the association between PON exposure, efficacy, and safety, and response-based dose reduction in pts with CP-CML. Methods: This ongoing, multicenter, randomized phase 2 trial enrolled pts with CP-CML resistant or intolerant to ≥2 TKIs or with a T315I mutation to receive PON at a starting dose of 45 mg (cohort A), 30 mg (B), and 15 mg (C) qd. Doses were reduced to 15 mg qd on achievement of ≤1% BCR-ABL1IS in A/B. Primary endpoint: 12 mo ≤1% BCR-ABL1IS; secondary endpoints include cytogenetic and molecular response and AOE, VTE, and TEAE rates. Results are descriptive at this IA and will be inferential by adjusting multiplicity across 3 cohorts at final analysis. Results: 283 pts were randomized (A/B/C: n = 94/95/94); median age 48 y (18‒81 y). 26% had hypertension history; 2/43/55% received 1/2/≥3 TKIs; 40% had ≥1 baseline (BL) mutations, with 23% T315I. At IA data cutoff (20 Jul 2019), 162 pts (57%; n = 57/51/54) remained on study treatment. Among 282 pts in the safety population, median duration of exposure was ≈1 y (A/B/C, 12.9/11.2/11.0 mo). At 12 mo, 39% (95% CI, 27.6, 50.6), 27% (17.6, 39.1), and 26% (16.5, 38.6) in A, B, and C, respectively, achieved ≤1% BCR-ABL1IS. Additional efficacy in Table. Dose reductions due to efficacy (A/B): 35/21%. Most common TEAEs (any grade/≥3): thrombocytopenia 39/27%, neutropenia 25/17%. AOEs/serious AOEs were reported by (A, B, C) 5%/2%, 4%/3%, and 1%/0%. Dose reductions due to TEAEs: (A/B/C): 44/31/28%; discontinuations due to TEAEs: 18/15/14%. There were 4 (1.4%) on-study deaths; A, sudden death, n = 2; C, pneumonia, n = 2; no deaths were due to AOEs. Clinical trial information: NCT01207440 . Conclusions: OPTIC IA shows a trend toward dose-dependent efficacy and safety and may provide a refined understanding of the PON benefit:risk profile and its relation to dose. Data from longer follow-up may support an alternate dosing regimen for pts with CP-CML. [Table: see text]

SUMMARY The diversity and heterogeneity within high-grade serous ovarian cancer (HGSC), which is the most lethal gynecologic malignancy, is not well understood. Here, we perform comprehensive multi-platform omics analyses, including integrated analysis, and immune monitoring on primary and metastatic sites from highly clinically annotated HGSC samples based on a laparoscopic triage algorithm from patients who underwent complete gross resection (R0) or received neoadjuvant chemotherapy (NACT) with excellent or poor response. We identify significant distinct molecular abnormalities and cellular changes and immune cell repertoire alterations between the groups, including a higher rate of NF1 copy number loss, and reduced chromothripsis-like patterns, higher levels of strong-binding neoantigens, and a higher number of infiltrated T cells in the R0 versus the NACT groups., Graphical Abstract, In Brief High-grade serous ovarian cancer (HGSC) patients with no gross residual disease (R0) after primary surgery have the greatest improvement in clinical outcomes. A deep understanding of molecular and cellular heterogeneity of HGSC is lacking. Findings by Lee et al. highlight major molecular and cellular differences between clinically defined subgroups of HGSC.

Background: Multiple myeloma (MM) is one of the most common malignancies found in hematology. Aim: To describe the features of patients with MM and perform a survival analysis according to the different treatment protocols used between 2000 and 2016. Material and Methods: Analysis of the database of the Chilean national anti-neoplastic drug program. Information was obtained from 1,103 patients, with a median age of 64.5 years (range 27-95) and a male to female ratio of 1:1.2. Results: The mean overall survival (OS) of patients receiving or not receiving Thalidomide was 46 and 30 months, respectively (p < 0.01). The mean OS of patients treated before 2007 (treated with melphalan and prednisone) and between 2007 and 2012 (treated with thalidomide and dexamethasone) was 36 and 48 months respectively. In the group starting in 2013 (treated with cyclophosphamide, thalidomide and dexamethasone) the median survival had not been reached at 20 months of follow up (p = 0.01 for all comparisons). Autologous transplantation (AT) was carried out in only 18% of the eligible patients. The median OS of the patients who receive an AT had not been reached at 48 month compared with 36 month among those who did not received the procedure (p < 0.01). Conclusions: Even though overall survival has improved with time, new drugs must be introduced in our protocols to obtain similar results to those obtained worldwide.

Multiple myeloma (MM) is one of the most common malignancies found in hematology.To describe the features of patients with MM and perform a survival analysis according to the different treatment protocols used between 2000 and 2016.Analysis of the database of the Chilean national anti-neoplastic drug program. Information was obtained from 1,103 patients, with a median age of 64.5 years (range 27-95) and a male to female ratio of 1:1.2.The mean overall survival (OS) of patients receiving or not receiving Thalidomide was 46 and 30 months, respectively (p0.01). The mean OS of patients treated before 2007 (treated with melphalan and prednisone) and between 2007 and 2012 (treated with thalidomide and dexamethasone) was 36 and 48 months respectively. In the group starting in 2013 (treated with cyclophosphamide, thalidomide and dexamethasone) the median survival had not been reached at 20 months of follow up (p = 0.01 for all comparisons). Autologous transplantation (AT) was carried out in only 18% of the eligible patients. The median OS of the patients who receive an AT had not been reached at 48 month compared with 36 month among those who did not received the procedure (p0.01).Even though overall survival has improved with time, new drugs must be introduced in our protocols to obtain similar results to those obtained worldwide.

Background: Intensified treatment of Philadelphia chromosome negative acute lymphoblastic leukemia (Ph(-)ALL) in adolescents by pediatric teams, with fve years disease free survival (DFS) rate of 65%, encouraged the use of intensified protocols in patients between 15 and 30 years, improving the DFS from 45% to 60-80%. The protocol LLA 15-30 for patients between 15 and 30 years with Ph(-)ALL, based on the Children’s Oncology Group (COG) protocol AALL0232 resulting in a five years DFS of 78%, was started in 2007 by the PANDA national program. Aim: To report the results of the prospective cohort study evaluating the results of this protocol four years after its implementation. Patients and Methods: Between January 2007 and December 2010, 68 Ph(-) ALL patients, aged between 15-30 years (75% males) were incorporated. Survival was evaluated using Kaplan-Meier and log-rank tests. Results: Fifty percent of patients were of high risk. A complete response was achieved in 91%, early death occurred in 6% and induction failure in 3%. Median follow-up was 23 months. Overall survival, disease free survival and relapse rates at 35 months were 61.8, 67.5% and 31% respectively. Conclusions: LLA 15-30 protocol significantly improved three-year overall survival from 31 to 62%. The 20% difference observed with AALL0232 protocol is explained by the high rate of relapse. Improving provider and patient compliance with protocols may eliminate this gap.

Background : Adult T-cell leukemia/lymphoma (ATLL) is an aggressive, peripheral T-cell neoplasm associated with the human T-cell leukemia virus type 1 (HTLV-1). HTLV-1 infects up to 10 million people worldwide and is most endemic in Southwestern Japan, the Caribbean basin, South America and Western Africa. In Latin America, highest prevalence is found in Haiti, Jamaica, Dominican Republic, Brazil and Peru. ATLL has a poor prognosis, with shorter overall survival (OS) relative to other peripheral T-cell lymphomas. Although current prognostic models require extensive radiologic and laboratory investigations, oftentimes they are not readily available in most Latin American countries, hence, a simple prognostic model is useful. We aim to identify and then validate a simple clinical prognostic model for ATLL in the Latin American population by analyzing clinical parameters and only laboratory tests that are widely available across Latin American countries. Patients and Methods : We retrospectively analyzed patients (pts) diagnosed with ATLL between January 1987 and December 2018. Aggressive ATLL cases were classified according to the Shimoyama criteria into acute (A) and lymphomatous (L). Cox regression modeling was performed on several clinical and laboratory parameters in two independent cohorts: first, a learning cohort (LC) of ATLL pts diagnosed and managed at two tertiary hospitals in Chile and Peru, and then a cohort of ATLL pts from a tertiary hospital in Miami was used to validate the model (validation cohort, VC). OS curves were estimated using the Kaplan-Meier method and compared using the log-rank test. Univariate and multivariate Cox proportional-hazard regression models were fitted. Results : A total of 149 pts (A=55, L=94) in the LC, and 101 pts (A=58, L=43) in the VC were identified, with 101 and 94 pts receiving therapy in each cohort, respectively. Clinical features are shown in Table 1. In both cohorts, there was a young ( In the univariate and multivariate analysis, ECOG ≥2 and serum albumin Conclusions : To the best of our knowledge, this is the largest retrospective study evaluating the clinical features of HTLV-1 related ATLL and impact on disease outcome in Latin America. We have validated a simple prognostic model in pts with aggressive ATLL. Our results suggest that a serum albumin level of less than 3.5 g/dL is a reliable, and independent prognostic factor for survival in aggressive ATLL. This prognostic model could be used to complement or modify existing and widely used international prognostic indexes for lymphoma. This simple paradigm could be useful in validating treatment outcomes after chemotherapy or highly needed new approaches for ATLL in prospective studies, particularly in developing countries where the absence of sophisticated laboratory and imaging tests hinder treatment decisions. Disclosures Peña: Novartis: Other: Congress inscription and flights; Tecnofarma: Other: Congress inscription and flights; Roche: Other: Congress inscription and flights; Biotoscana: Other: Congress inscription and flights; Janssen: Other: Congress inscription and flights; Pfizer: Membership on an entity's Board of Directors or advisory committees. Rojas:Pfizer: Membership on an entity's Board of Directors or advisory committees; ABBVIE: Membership on an entity's Board of Directors or advisory committees; NOVARTIS: Membership on an entity's Board of Directors or advisory committees; ROCHE: Membership on an entity's Board of Directors or advisory committees. Paredes:Tecnofarma: Honoraria. Abello:Takeda: Other: Participation in advisory board meeting. M:Merck-Sharp-Dome: Speakers Bureau; Takeda: Consultancy, Speakers Bureau; Roche-Mexico: Consultancy, Speakers Bureau.