denotes an abstract that is clinically relevant.
denotes that this is a recommended PHD Trainee Session.
denotes that this is a ticketed session.Session: 637. Myelodysplastic Syndromes: Clinical and Epidemiological: Poster III
Hematology Disease Topics & Pathways:
Research, Clinical trials, MDS, Adult, Clinical Research, Chemotherapy, Genetic Disorders, Chronic Myeloid Malignancies, Diseases, Treatment Considerations, Non-Biological therapies, Myeloid Malignancies, Study Population, Human
Methods. Patients with R/R or treatment-naïve (TN) mIDH1 MDS (intermediate, high or very-high risk by IPSS-R) were included. Olutasidenib was given at 150 mg BID or 100-150 mg QD as monotherapy, or as a combination of olutasidenib 150 mg BID plus azacitidine (75 mg/m2 daily x 7 days/28-day cycles). The primary efficacy endpoints were safety (phase 1) and complete remission (CR; based on IWG in MDS 2006) rates. Secondary endpoints included overall response (CR/partial remission [PR]/marrow CR), time to response (TTR), duration of response (DOR), and safety (phase 2).
Results. At data cut-off (16 June 2023), 22 patients with MDS were included from the phase 1/2 studies; 6 received monotherapy (4 R/R, 2 TN) and 16 received combination therapy (11 R/R, 5 TN). Median age was 74 (range 59-87) years; 59% were male, and 86% had baseline ECOG of 0 or 1. MDS was high-risk in 68% and very high-risk in 18%. Patients had had a median of 1 (range 1-4) prior regimen for MDS; 64% had a prior hypomethylating agent and 1 had a prior stem cell transplant.
For the pooled phase 1/2 data, overall response rate (ORR) was 59% (CR: 27%; marrow CR: 32%). ORR with monotherapy was 33% (CR: 17%; marrow CR: 17%), including 2/3 (66%) with the approved dose of 150 mg BID and 0/3 with the lower doses of 100-150 mg QD, and ORR with combination therapy was 11/16 (69%). Median TTR was 2.0 months. Median DOR was 14.6 months (range 0.0 to 52.0), and median duration of CR was 20.5 months (range 0.0 to 52.0). Overall survival was 27.2 months (range 0.0 to 67.0). Three patients proceeded to stem cell transplant.
Of 7 patients (32%) experiencing marrow CR (mCR), 4 (57%) experienced hematological improvement in ≥1 lineage (erythrocyte, platelet and/or neutrophil); 3 (43%) had an improvement in erythrocyte counts, 3 (43%) in platelet counts, and 4 (57%) in neutrophil counts (mIWG 2006 response criteria).
In a subanalysis of the 19 efficacy evaluable patients,11/14 (79%) responded to combination therapy and 2/5 (40%) responded to monotherapy, which included 2/2 (100%) using the approved dose of 150 mg BID olutasidenib.
All patients reported adverse events (AEs), and the most common were fatigue, nausea, constipation, arthralgia, decreased platelet counts, and vomiting. Grade 3 and Grade 4 AEs occurred in 19 (86%) and 9 (41%) patients, respectively; cytopenias were most frequently reported. Differentiation syndrome occurred in 3 patients (Grade 3 in 1 patient). Grade 3 or 4 elevation in alanine transaminase occurred in 3 (14%) patients.
Conclusions. Patients with intermediate- to very high-risk mIDH1 MDS treated with olutasidenib monotherapy or in combination with azacitidine demonstrated encouraging response rates with durable remissions and an acceptable and manageable safety profile.
Disclosures: Cortes: Pfizer: Consultancy; Sun Pharma: Consultancy, Research Funding; Syndax: Consultancy; AbbVie: Research Funding; Nerviano: Consultancy; Lilly: Consultancy; Biopath Holdings: Consultancy, Current holder of stock options in a privately-held company, Membership on an entity's Board of Directors or advisory committees; Ascentage: Research Funding; Novartis: Consultancy, Research Funding; Rigel: Consultancy. Watts: Reven Pharma: Consultancy; Rafael Pharma: Consultancy; Immune Systems Key: Research Funding; Takeda: Research Funding; Celgene/BMS: Consultancy; Aptose: Consultancy, Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo: Consultancy; Incyte: Research Funding; Servier: Consultancy, Membership on an entity's Board of Directors or advisory committees; Rigel: Consultancy, Other: safety monitoring or advisory boards, Research Funding. Wang: Immunogen: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Syndax: Membership on an entity's Board of Directors or advisory committees; Kite: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees; Qiagen: Membership on an entity's Board of Directors or advisory committees; Stemline: Membership on an entity's Board of Directors or advisory committees; Sumitomo Pharma: Membership on an entity's Board of Directors or advisory committees; J&J: Membership on an entity's Board of Directors or advisory committees; Kura: Speakers Bureau; UptoDate: Other: Section Editor; Mana: Membership on an entity's Board of Directors or advisory committees; PharmaEssentia: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; NuProbe: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sellas: Membership on an entity's Board of Directors or advisory committees; Schrodinger: Membership on an entity's Board of Directors or advisory committees; Rigel: Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo: Membership on an entity's Board of Directors or advisory committees; CTI Biopharma: Membership on an entity's Board of Directors or advisory committees; Blueprint: Membership on an entity's Board of Directors or advisory committees; Dava Oncology: Speakers Bureau; Jazz: Consultancy, Membership on an entity's Board of Directors or advisory committees; Astellas: Consultancy, Speakers Bureau; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; GSK: Consultancy, Membership on an entity's Board of Directors or advisory committees; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Data Safety Monitoring Committee, Award Committee, Research Funding; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Data Safety Monitoring Committee, Research Funding, Speakers Bureau. Yang: Novartis: Consultancy, Research Funding; Pfizer: Research Funding; Puretech: Research Funding. Dinner: Pfizer: Consultancy; Rigel: Consultancy; Kite: Consultancy. Roboz: Janssen: Research Funding; AbbVie, Amgen, Astrazeneca, Caribou Biosciences, Celgene, Daiichi Sankyo, Ellipses pharma, Geron, GSK, Glycomimetics, Janssen, Jasper Pharmaceuticals, Jazz Pharmaceuticals, Molecular Partners, Oncoverity: Consultancy; OncoPrecision: Current holder of stock options in a privately-held company, Honoraria; Novartis, Pfizer, Roche, GlaxoSmithKline, BMS, Syndax, Rigel: Consultancy.
OffLabel Disclosure: Olutasidenib, indicated for relapsed or refractory acute myeloid leukemia with a susceptible IDH1 mutation
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