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.

Extramedullary spread of multiple myeloma was thought to be uncommon but with recent advancements in imaging and increased patient survival, the incidence of the extraosseous disease has risen in living individuals. Despite this, the extraosseous spread of multiple myeloma has been under-diagnosed and under-reported. Timely diagnosis of this extraosseous disease is clinically important, as it indicates a more aggressive disease variant and carries a poor prognosis.

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]

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.

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 <15% (n=172) and SF3B mutation were present in 169 evaluable patients. Low-risk MDS (LR-MDS) patients are classified according to IPSS-R criteria, defined as being of very low (n=19), low (n=135), or intermediate-risk (n=44). Platzbecker et al. (2017) studied luspatercept in MDS patients (n=58) in the PACE phase II trial. Fenaux et al. (2020) studied the efficacy of luspatercept in MDS pts (n=219) in the MEDALIST phase III trial. The baseline Erythropoietin (EPO) levels were: levels <200: n=191, level 200-500: n= 81, level >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.