Session: 637. Myelodysplastic Syndromes: Clinical and Epidemiological: Poster I
Hematology Disease Topics & Pathways:
MDS, Clinical Practice (Health Services and Quality), Chronic Myeloid Malignancies, Diseases, Myeloid Malignancies
Methods: This Phase 2 trial (NCT04419649) enrolled participants with International Prognostic Scoring System-Revised (IPSS-R) Very Low-, Low-, or Intermediate-risk MDS. Analyses included participants receiving the recommended Part 2 dose (3.75 up to 5 mg/kg, N=87) as of data cut off (DCO) of 03Apr2024. Rates of TI≥8 wks and ≥24 wks were analyzed over the first 24 and 48 wks of treatment in a modified intent-to-treat-24 (mITT24) population, including participants who received ≥2 RBC units in the 8 wks before treatment and received ≥24 wks of treatment or discontinued (N=63). Durability of TI was assessed using Kaplan-Meier (KM) estimation. QoL was assessed using the Functional Assessment of Cancer Therapy-Anemia (FACT-An; 47 item) at baseline and after approximately 4, 8, 12, 16, and 24 wks of treatment. Domains of FACT-An including physical (7-item), functional (7-item), social (7-item), emotional (6-item) well-being, the anemia subscale (AnS, 20-item), and FACIT-Fatigue (13-item) were analyzed separately.
Results: Among mITT24 TI-evaluable participants, 41.3% achieved TI≥8 wks in the first 24 wks of elritercept treatment, including participants with non-RS (ring sideroblasts) and/or high transfusion burden. Responses were durable, with 61.5% of TI≥8 wks participants maintaining TI as of the DCO, and the median duration of response was not reached. Additionally, 25.4% of evaluable mITT24 participants achieved TI≥24 wks over the first 48 wks of treatment, and among TI≥8 wks responders, the proportion who maintained TI≥24 wks was 61.5%.
Improvements in QoL based on FACT-An total score were observed in TI responders vs non-responders and increased with greater duration of TI. At wk 24, mean increases in FACT-An total score were greater for TI≥24 wks (13.1, minimally clinically important difference [MCID] = 7) compared to TI≥8 wks responders (4.8) as was the separation vs non-responders (mean difference vs non-responders for TI≥8 and TI≥24 responders were 5 and 16.1 [>2-fold the MCID], respectively). Of the FACT-An domains, differences in AnS score, especially the FACIT-Fatigue component, were major drivers for improvements observed in TI≥24 wks vs TI≥8 wks responders. Baseline FACIT-Fatigue scores for TI≥8 / TI≥24 responders were 28.4 / 28.2 vs. non-responders 30.4 / 30.0 indicating similar level of fatigue in both populations. At wk 24, mean increases from baseline in fatigue score were greater for TI≥24 (6.6, MCID = 3) compared to TI≥8 wks responders (2.0), as was the separation vs non-responders (mean difference vs non responders for TI≥8 / TI≥24 responders = 3.2/ 9.4 [>3-fold the MCID]). FACIT-Fatigue scores improved over time in TI≥24 wk responders; mean increases of 2.9 were observed at wk 4 and reached 6.6 by wk 24. Similarly, the proportion of TI≥24 wk responders vs non-responders whose change in FACIT-Fatigue met the MCID was 54% vs 20% at wk 4, improving to 75% vs 16% at wk 24. Items driving observed improvements in FACIT-Fatigue score were related to both fatigue experience and fatigue impact.
Summary: These findings support the potential for elritercept to produce durable TI that is associated with clinically meaningful improvements in QoL, thus addressing important goals in treating LR-MDS. Fatigue burden (both experience and impact) was a primary driver of the observed improvements in QoL in TI responders vs non-responders. Importantly, clinically meaningful improvements in fatigue scores were observed early and continued to improve over time in participants with more durable TI responses.
Disclosures: Giagounidis: Amgen: Consultancy; BMS: Consultancy. Arnan: Keros: Consultancy. Chee: Otsuka: Honoraria, Membership on an entity's Board of Directors or advisory committees; Keros Therapeutics: Consultancy, Honoraria; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees. Cluzeau: Abbvie: Consultancy, Research Funding, Speakers Bureau; Jazz Pharma: Consultancy, Research Funding, Speakers Bureau; Takeda: Speakers Bureau; BMS: Consultancy, Speakers Bureau; Amgen: Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Keros: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte: Speakers Bureau; Syros: Speakers Bureau; Servier: Consultancy, Speakers Bureau; Pfizer: Other: International Congress. Diez-Campelo: Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; AGIOS: Consultancy, Membership on an entity's Board of Directors or advisory committees; SYROS: Membership on an entity's Board of Directors or advisory committees; KEROS: Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS/Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Advisory board fees; Gilead: Other: Travel reimbursement; CURIS: Membership on an entity's Board of Directors or advisory committees; GSK: Consultancy, Membership on an entity's Board of Directors or advisory committees; BLUEPRINT MEDICINES: Consultancy, Membership on an entity's Board of Directors or advisory committees; ASTEX/OTSUKA: Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL TO MEETINGS; HEMAVAN: Membership on an entity's Board of Directors or advisory committees. Hiwase: Abbvie: Honoraria; Astella Pharma: Honoraria; Otsuka: Honoraria. Ross: Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Keros: Membership on an entity's Board of Directors or advisory committees; Merck: Honoraria, Membership on an entity's Board of Directors or advisory committees; Menarini: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees. Sekeres: Kurome: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Research Funding; Schroedinger: Membership on an entity's Board of Directors or advisory committees. Valcarcel: Bristol Myers Squibb/Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Meeting and travel accommodation, Research Funding, Speakers Bureau; Astellas: Consultancy, Honoraria; TAKEDA: Consultancy, Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Meeting and travel accommodation, Speakers Bureau; MSD: Consultancy, Honoraria, Speakers Bureau; Kite/Gilead: Consultancy, Honoraria, Speakers Bureau; Jazz Pharmaceuticials: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Meeting and travel accommodation, Speakers Bureau; Janssen: Honoraria, Speakers Bureau; SOBI: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Meeting and travel accommodation, Speakers Bureau; Pfizer: Honoraria, Speakers Bureau; Servier: Membership on an entity's Board of Directors or advisory committees; Sanofi: Consultancy, Honoraria, Other: Meeting and travel accommodation, Speakers Bureau; Agios: Honoraria, Other: Meeting and travel accommodation, Speakers Bureau; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Meeting and travel accommodation, Speakers Bureau; AbbVie: Consultancy, Other: Meeting and travel accommodation; Gebro: Honoraria, Speakers Bureau; Grifols: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Meeting and travel accommodation, Speakers Bureau. Buckstein: Abbvie: Honoraria; BMS: Honoraria, Research Funding; Taiho: Honoraria, Research Funding; Keros: Other: Advisory Board. Patel-Shah: Keros: Current Employment. Yang: Keros: Current Employment. Jiang: Keros: Current Employment. Yin: Keros: Current Employment. Bobba: Keros: Current Employment. Hankin: Keros: Current Employment. Materna: Keros: Current Employment. Graham: Keros: Current Employment. Thamake: Keros: Current Employment. Rovaldi: Keros: Current Employment. Grayson: Keros: Current Employment. Salstrom: Keros: Current Employment.
See more of: Oral and Poster Abstracts