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1867 Hematological Response to Frontline Treatment in Lower Risk Myelodysplastic Syndromes (LRMDS) Is Associated with Better Overall Survival

Program: Oral and Poster Abstracts
Session: 637. Myelodysplastic Syndromes – Clinical and Epidemiological: Poster I
Hematology Disease Topics & Pathways:
Research, MDS, Clinical Research, Chronic Myeloid Malignancies, patient-reported outcomes, Diseases, real-world evidence, Myeloid Malignancies
Saturday, December 9, 2023, 5:30 PM-7:30 PM

Rami S. Komrokji, MD1, Muhammad Ammad-ud-din, MD1*, Najla H Al Ali, MS1*, Zhuoer Xie, MD, MS1, Onyee Chan, MD1*, Andrew T. Kuykendall, MD1, Seongseok Yun, MD, PhD1, Alison R. Walker, MD, MPH, MBA1, Jeffrey Lancet, MD1, Eric Padron, MD1 and David A Sallman, MD2

1Department of Malignant Hematology, Moffitt Cancer Center, Tampa, FL
2H. Lee Moffitt Cancer Center, Tampa, FL


The majority of LRMDS patients (pts) (70%) do not progress but unfortunately succumb to complications related to cytopenia, namely anemia and red blood cell transfusion dependency (RBC-TD) or their interplay with co-morbidities. RBC-TD is associated with worse outcome reflecting bone marrow failure and long-term sequela of RBC-TD. There is growing evidence that response to treatment and RBC transfusion independence (TI) are associated with favorable outcome. In lieu of 2 recent randomized clinical trials demonstrating efficacy of luspatercept & imetelstat in LRMDS, we assessed the impact of response to sequential lines of treatment in LR-MDS on overall survival (OS) to guide our treatment choices and to determine whether erythroid stimulating agents (ESA) should still be our 1st line of therapy.


We included LRMDS pts (IPSS-R very low & low) from Moffitt Database who received ESA as frontline therapy (FL) and assessed subsequently outcomes with second line (SL) therapy (SOC or clinical trial). We excluded MDS/MPN and del5q pts. We also excluded all pts who eventually progressed to either higher risk MDS or AML to better reflect the majority LRMDS in that disease state. We assessed details of FL and SL. Pts who received FL & SL were then divided into 4 groups based on response to FL and SL therapy: group 1 (no/no), group 2 (no/yes) with response only to SL, group 3 (yes/no) response to FL only, and group 4 (yes/yes) with response to both lines of therapy. Response was defined as hematological improvement (HI) with ≥1.5 g/dl Hgb increase in non-TD pts and RBC-TI in TD pts at baseline for at least for 8 weeks. We compared median OS (mOS) among those groups.


There were 603 LRMDS pts who met eligibility criteria and received ESA as FL (Table-1); 43% were RBC-TD, mean serum EPO was 132 (n=211 pts), 69% received epoetin, 17% darbepoetin and 14% with G-CSF. HI was observed in 42% of pts with no difference among ring sideroblasts (RS) +/- (46% vs 40%, p =.12). Response was higher among non-RBC-TD (52% vs 31%, p< .001). The median time to start ESA was 1.2 mo (0-249). The median time on ESA therapy was 11 mo (.4-213).

331 pts (55%) received SL which included HMA 43% (n= 142), lenalidomide 39% (n=130), luspatercept 7% (n=24), ATG 2% (n=8), investigational agent 4% (n=14), and other 4% (n=13) . The HI rate was 27% (91/331). No difference in HI based on RS nor RBC-TD was observed. The median duration on SL treatment was 6 mo (.1-93).

170 pts (28%) received 3rd line of therapy with 7% HI, 88 pts (15%) received 4th line of therapy with 3% HI and 39 pts (7%) had 5th line of therapy with 2% HI.

Among the 331 pts who received at least FL and SL, pts were divided into 4 groups based on response to (methods, table-2), the mOS was 114 mo among Yes/Yes response group, 103 mo among yes/no group, 97 mo no/yes and 64 mo among no/no ( P=.007; Figure-1). Response to FL was significantly associated with better OS after adjusting for RS (HR .74 ,95% CI .55-.99, p=.043).


Only half of patients who receive ESA as FL therapy for LRMDS received any subsequent therapies. Response rates were highest with ESA as FL than any SL therapy. HI with FL and/or SL is associated with improved OS. Lack of response to first line of therapy is associated with worse OS. Responses beyond SL were rarely observed. Identifying and moving agents with high HI rate as FL therapy and or selecting option based on predictors of best chance of response to a specific treatment as FL may lead to better overall survival.

Disclosures: Komrokji: BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Rigel, Taiho, DSI: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; AbbVie, CTI biopharma, Jazz, Pharma Essentia, Servio: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Geron: Consultancy. Kuykendall: Sierra Oncology: Research Funding; AbbVie: Consultancy; Blueprint: Consultancy, Research Funding, Speakers Bureau; Morphosys: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Prelude: Research Funding; Protagonist Therapeutics, Inc.: Consultancy, Research Funding; CTI: Consultancy; GSK: Consultancy; Imago: Consultancy; Incyte: Consultancy; Novartis: Consultancy. Lancet: Jasper Therapeutics: Consultancy; Celgene: Consultancy, Research Funding; Tegus: Consultancy; Servier: Consultancy; Jazz: Consultancy; Boxer Capital: Consultancy; The Dedham Group: Consultancy; Globe Life Sciences: Consultancy; Peer Voice: Consultancy; MD Anderson: Consultancy; Novartis: Consultancy; BerGenBio / DAVA Oncology: Consultancy; Atheneum: Consultancy; AbbVie Inc.: Consultancy; MEDTalks: Consultancy. Padron: Gillead: Membership on an entity's Board of Directors or advisory committees; CTI: Membership on an entity's Board of Directors or advisory committees; Pharmaessentia: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Kura: Research Funding; Incyte: Research Funding; BMS: Research Funding. Sallman: Aprea, Jazz: Research Funding; AbbVie, Affimed Gmbh, Gilead, Incyte, Intellisphere, LLC, Molecular Partners AG, PGEN Therapeutics, Inc., Takeda, Zentalis; Advisory board for AvenCell, BlueBird Bio, BMS, Intellia, Jasper Therapeutics, Kite, Magenta Therapeutics, NKARTA, Novartis, Orbita: Consultancy.

*signifies non-member of ASH