Clinical Effectiveness of Hypomethylating Agents (HMAs) and Lenalidomide (Len) in Older Patients (pts) with Refractory Anemia with Ring Sideroblasts: A Large Population-Based Study in the United States (US)

Introduction: Refractory anemia with ring sideroblasts (RARS) is a subtype of low risk (LR)-MDS marked by accumulation of abnormal erythroid precursors with iron-filled mitochondria in a ringed pattern around the nucleus. HMAs (azacitidine, AZA; decitabine, DEC) are approved for the treatment of MDS pts in the US and predominantly used for pts with high risk MDS, while Len is approved for treating pts with red blood cell (RBC) transfusion-dependent (TD), deletion 5q (del5q) LR-MDS. As anemic pts with non-del5q LR-MDS often do not respond or eventually stop responding to erythropoiesis-stimulating agents, HMAs and Len are often used in these pts as well. While there is clinical trial and population-based studies supporting clinical effectiveness of HMAs and Len in pts with non-del5q LR-MDS, data regarding activity of these agents in pts with RARS are very limited. Understanding the clinical effectiveness of the agents available in the market in RARS is especially important as new agents for this pt population might enter the market (e.g. luspatercept). We conducted a large population-based study to examine the use of HMAs and Len in lower-risk non-del5q MDS pts, stratifying by RS status. Methods: Using the Surveillance, Epidemiology, and End Results-Medicare linked database, we assembled a cohort of older adults (66-99 years) diagnosed with non-del5q LR-MDS during 2007-15 with continuous Medicare Parts AB after a median of 13 (IQR 11-26) weeks, 53.8% became TI. Among 204 non-RS pts who used HMA only, 36.8% were TD at initiation; after a median of 15 (IQR 11-19) weeks, 57.3% became TI. Median duration of transfusion independence was 13 (IQR 2-50) and 21 (4-43) weeks, respectively, for RS and non-RS pts who became TI. Among pts who only received Len, 41.5% of RS and 39.1% of non-RS pts were TD, with more than 40% changing from TD to TI in both groups after a median of 20 weeks. Median OS was 2.8 and 2.1 years for RARA and no-RS pts, respectively (log-rank p Conclusions: In this large, population-based study of older adults with non-del5q LR-MDS, our results suggest that HMAs and lenalidomide are clinically active in pts with RARS. While the RBC transfusion independence rate with HMAs (54%) was somewhat higher than was reported for luspatercept (38%), the median duration appears shorter (13 vs 31 weeks). However, these numbers are limited by small sample size and more research is needed to understand the comparative clinical effectiveness for therapies that target anemia in pts with RARS. Download : Download high-res image (872KB) Download : Download full-size image Disclosures Wang: Celgene Corporation: Research Funding. Zeidan: Cardinal Health: Honoraria; Daiichi Sankyo: Honoraria; Abbvie: Consultancy, Honoraria, Research Funding; Acceleron Pharma: Consultancy, Honoraria, Research Funding; BeyondSpring: Honoraria; Celgene Corporation: Consultancy, Honoraria, Research Funding; Otsuka: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; Medimmune/AstraZeneca: Research Funding; Boehringer-Ingelheim: Consultancy, Honoraria, Research Funding; Trovagene: Consultancy, Honoraria, Research Funding; Incyte: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; ADC Therapeutics: Research Funding; Jazz: Honoraria; Ariad: Honoraria; Agios: Honoraria; Novartis: Honoraria; Astellas: Honoraria; Seattle Genetics: Honoraria. Podoltsev: Sunesis Pharmaceuticals: Research Funding; Jazz Pharmaceuticals: Research Funding; Arog Pharmaceuticals: Research Funding; Genentech: Research Funding; Daiichi Sankyo: Research Funding; Kartos Therapeutics: Research Funding; Boehringer Ingelheim: Research Funding; AI Therapeutics: Research Funding; Samus Therapeutics: Research Funding; Alexion: 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; Astellas Pharma: Research Funding; Pfizer: Research Funding; Agios Pharmaceuticals: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Blueprint Medicines: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Incyte: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Astex Pharmaceuticals: Research Funding; CTI Biopharma: Research Funding; Celgene: Other: Grant funding, Research Funding. Huntington: Bayer: Consultancy, Honoraria; Pharmacyclics: Honoraria; DTRM Biopharm: Research Funding; AbbVie: Consultancy; Celgene: Consultancy, Research Funding; Genentech: Consultancy. Gore: Celgene Corporation: Consultancy, Research Funding. Davidoff: Celgene Corporation: Consultancy, Research Funding.