Session: 637. Myelodysplastic Syndromes: Clinical and Epidemiological: Poster III
Hematology Disease Topics & Pathways:
Research, MDS, Clinical Research, Chronic Myeloid Malignancies, Diseases, Myeloid Malignancies
Methods: We retrospectively evaluated all MDS patients treated with frontline HMA-based therapy at multiple cancer centers in the United States and Europe. Patient characteristics and bone marrow (BM) data were assessed at diagnosis. Median overall survival (OS) and leukemia-free survival (LFS) were analyzed using the Kaplan-Meier method with log-rank tests comparing groups. Model discrimination was evaluated using the Harrell concordance index (c-index).
Results: A total of 1838 MDS patients underwent treatment with HMA and had available IPSS-M risk stratification data. At diagnosis, the median age was 70 years (range: 19-94) and 1189 (65%) were male. Patients generally had high risk disease, including therapy-related MDS in 422/1511 (28%), complex cytogenetics in 582 (32%), and TP53 mutations in 444 (28%). By IPSS-R, 1180 patients (64%) had high- or very high-risk disease. By IPSS-M, 1506 patients (82%) had higher-risk disease (moderate high-, high-, and very high-risk). A total of 1542/1811 patients (85%) were treated with HMA monotherapy.
By IPSS-R, the median OS was 60.0 months (mos) (95% CI: 46.0, not estimable (NE)) in 15 very low-, 71.2 mos (95% CI: 63.4, 114.8) in 152 low-, 38.0 mos (95% CI: 33.5, 44.8) in 482 intermediate-, 27.3 mos (95% CI: 24.3, 32.0), in 521 high-, and 14.8 mos (95% CI: 13.9, 16.3) in 659 very high-risk patients (p<0.0001) with a c-index of 0.661. Risk stratification by IPSS-M provided similar results: not reached (95% CI: 88.0, NE) in 12 very low-, 66.5 mos (95% CI: 62.2, 131.3) in 159 low-, 53.2 mos (95% CI: 45.4, 70.0) in 161 moderate low-, 36.5 mos (95% CI: 30.7, 46.9) in 238 moderate high-, 26.1 mos (95% CI: 23.5, 30.9) in 529 high-, and 15.8 mos (95% CI: 14.8, 17.0) in 739 very high-risk patients (p<0.0001). The c-index of IPSS-M in all HMA-treated MDS patients was 0.669. Among patients with MDS who were more likely to receive HMA per standard-of-care treatment (IPSS-R score >3.5), the IPSS-M remained statistically significant (p<0.0001) though less discerning, demonstrated by a c-index of 0.639. When evaluating LFS, comparable results were obtained with IPSS-R (p<0.0001, c-index 0.650) and IPSS-M (p<0.0001, c-index 0.657) for the entire cohort. For OS among subgroups, IPSS-M can well separate patients to different risk groups (p<0.001), but c-indices remained below 0.7 (normal karyotype: 0.660, complex cytogenetics: 0.604, therapy-related MDS: 0.638, TP53 mutated: 0.587, wild-type TP53: 0.656, and alloSCT recipients: 0.643).
Patients were stratified into lower-risk and higher-risk groups by IPSS-R (IPSS-R score ≤3.5 and >3.5, respectively) and IPSS-M. The median OS was 66.5 mos (95% CI: 62.2, 93.4) in IPSS-R lower-, 22.7 mos (95% CI: 21.7, 23.9) in IPSS-R higher-, 64.3 mos (95% CI: 59.3. 87.4) in IPSS-M lower-, and 21.0 mos (95% CI: 19.5, 22.3) in IPSS-M higher-risk patients. Twenty-nine (2%) patients were upstaged from IPSS-R lower- to IPSS-M higher-risk disease with a median OS of 35.6 mos (95% CI: 31.1, NE), and 35 (2%) patients were downstaged from IPSS-R higher- to IPSS-M lower-risk disease with a median OS of 43.0 mos (95% CI: 29.5, 71.4).
Conclusions: In this group of HMA-treated patients with MDS, the IPSS-M did not provide additional prognostic power over the IPSS-R, though median OS remained inversely proportional to IPSS-M risk category. Concordance indices for survival remained below 0.7 amongst all subgroups. Further development and validation of prognostic scoring systems in HMA-treated MDS patients are warranted.
Disclosures: Chien: Rigel Pharmaceuticals: Consultancy; AbbVie: Consultancy. Montalban-Bravo: Rigel: Research Funding; Takeda: Research Funding. Short: Sanofi: Honoraria; Amgen: Honoraria; Novartis: Honoraria; Stemline Therapeutics: Research Funding; Xencor: Research Funding; Takeda Oncology: Honoraria, Research Funding; GSK: Consultancy, Research Funding; NextCure: Research Funding; BeiGene: Honoraria; Autolus: Honoraria; Adaptive Biotechnologies: Honoraria; Astellas Pharma, Inc.: Honoraria, Research Funding; Pfizer Inc.: Honoraria. Jabbour: AbbVie, Adaptive Biotechnologies, Amgen, Ascentage Pharma Group, Pfizer, Takeda: Research Funding; AbbVie, Adaptive Biotechnologies, Amgen, Astellas Pharma, BMS, Genentech, Incyte, Pfizer, Takeda: Consultancy. Kadia: ASTEX: Research Funding; Incyte: Research Funding; Ascentage: Research Funding; AstraZeneca: Research Funding; Cellenkos: Research Funding; Abbvie: Consultancy, Research Funding; Pfizer: Research Funding; Amgen: Research Funding; Regeneron: Research Funding; DrenBio: Consultancy, Research Funding; Sellas: Consultancy, Research Funding; Rigel: Honoraria; Servier: Consultancy; JAZZ: Research Funding; Novartis: Honoraria; BMS: Consultancy, Research Funding; Genentech: Consultancy, Research Funding. Ravandi: Xencor: Research Funding; Abbvie: Consultancy, Honoraria; Astellas: Consultancy, Honoraria; Syros: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria; Prelude: Consultancy, Honoraria, Research Funding; Amgen: Research Funding; Astyex/Taiho: Research Funding; Syndax: Honoraria. Borthakur: Catamaran Bio, AbbVie, PPD Development, Protagonist Therapeutics, Janssen: Consultancy; Astex Pharmaceuticals, Ryvu, PTC Therapeutics: Research Funding; Pacylex, Novartis, Cytomx, Bio Ascend: Membership on an entity's Board of Directors or advisory committees. Swaminathan: Sobi: Consultancy, Membership on an entity's Board of Directors or advisory committees. Sasaki: Daiichi-Sankyo: Consultancy; Novartis: Consultancy, Research Funding; Enliven: Research Funding; Pfizer: Consultancy; Chugai: Other: Lecture fees; Otsuka: Other: Lecture fees. Sallman: Abbvie: Consultancy; Agios: Consultancy; Axiom: Consultancy; Gilead: Consultancy; Celyad: Consultancy; Froghorn: Consultancy; Incyte: Consultancy; Intellisphere, LLC: Consultancy; Johnson & Johnson: Consultancy; Kite: Consultancy, Membership on an entity's Board of Directors or advisory committees; Magenta Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; NextTech: Consultancy; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; AvenCell: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees; BlueBird Bio: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Dark Blue Therapeutics: Membership on an entity's Board of Directors or advisory committees; Intellia: Membership on an entity's Board of Directors or advisory committees; Jasper Therapeutics: Membership on an entity's Board of Directors or advisory committees; NKARTA: Membership on an entity's Board of Directors or advisory committees; Orbital Therapeutics: Membership on an entity's Board of Directors or advisory committees; Rigel Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Shattuck Labs: Membership on an entity's Board of Directors or advisory committees; Servier: Membership on an entity's Board of Directors or advisory committees; Syndax: Membership on an entity's Board of Directors or advisory committees; Syros: Membership on an entity's Board of Directors or advisory committees; Apera: Research Funding; Jazz: Research Funding. Kantarjian: AbbVie, Amgen, Ascentage, Ipsen Biopharmaceuticals, KAHR Medical, Novartis, Pfizer, Shenzhen Target Rx, Stemline,Takeda: Consultancy, Honoraria. Della Porta: Bristol Myers Squibb: Consultancy. Garcia-Manero: Astex: Research Funding; Forty Seven: Research Funding; Curis: Research Funding; Genentech: Research Funding; H3 Biomedicine: Research Funding; Janssen: Research Funding; Merck: Research Funding; Onconova: Research Funding; Bristol Myers Squibb: Other: Personal fees, Research Funding; AbbVie: Research Funding; Aprea: Research Funding; Astex: Other: Personal fees; Helsinn: Other: Personal fees; Genentech: Other: Personal fees; Amphivena: Research Funding; Novartis: Research Funding; Helsinn: Research Funding. Komrokji: Servio: Honoraria; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees; DSI: Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Research Funding; Janssen: Consultancy; Keros: Membership on an entity's Board of Directors or advisory committees; Servio: Membership on an entity's Board of Directors or advisory committees; Sumitomo Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sobi: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Rigel: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Jazz Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Geron: Consultancy, Membership on an entity's Board of Directors or advisory committees; Taiho: Membership on an entity's Board of Directors or advisory committees; PharmaEssentia: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; DSI: Consultancy, Membership on an entity's Board of Directors or advisory committees; Servier: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Genentech: Consultancy; Novartis: Membership on an entity's Board of Directors or advisory committees; CTI biopharma: Membership on an entity's Board of Directors or advisory committees; Celgene/BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees.
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