Session: 617. Acute Myeloid Leukemias: Commercially Available Therapies: Poster II
Hematology Disease Topics & Pathways:
Research, Clinical trials, Adult, Acute Myeloid Malignancies, AML, Combination therapy, Clinical Research, Genetic Disorders, Diseases, Treatment Considerations, Myeloid Malignancies, Study Population, Human
Methods: Adult patients with R/R mIDH1R132 AML received twice daily 150 mg OLU (in continuous 28-day cycles) plus standard-of-care AZA (daily for 7 consecutive days, in 28-day cycles) and were evaluated for safety and response.
Results: Sixty-seven patients with R/R mIDH1R132 AML received combination OLU+AZA after a median 10.2 months since AML diagnosis; 43% were refractory and 57% relapsed to prior treatment. Median age was 66 years (range 28-82), and 54% were male. Baseline ECOG was 0-1 in 82%. Most (83%) patients had 2+ prior treatment regimens, including HMA in 40%, IDH1 inhibitor therapy in 31% (olutasidenib monotherapy in 24%), and hematopoietic stem cell transplant (HSCT) in 10%. Cytogenetic risk class was intermediate in 72%, poor in 18% and unknown in 10%. One to 3 co-mutations were identified in 58% of patients, 4-7 in 19%, with FLT3 in 19% and TP53 in 6%.
CR/CRh was achieved in 21/67 (31%; 95% CI, 21-44) patients, and median duration of CR/CRh was 15 months (range 0.4-49). The median time to CR/CRh was 3 months (range 1-10). CR was achieved in 18/67 (27%; 95% CI, 17-39) patients with median duration of 20 months (range 0-44). Overall response (partial remission or better) was achieved in 34/67 (51%; 95% CI, 38-63) patients. In a subset analysis (N=51) excluding patients who had prior OLU exposure, CR/CRh was achieved in 19/51 (37%; 95% CI, 24-52) patients, and CR was achieved in 16/51 (31%; 95% CI, 19-46). Overall response was achieved in 30/51 (59%; 95% CI, 44-72). Duration of CR/CRh was identical for the subset of 51 patients to the full group of 67 patients.
The median overall survival was 13 months (95% CI, 9-19) in 67 patients, 24 months in overall responders, 30.6 months in patients with CR/CRh, and not reached (range 11.5, 55.3+) in patients with CR. Twelve patients (18%) who achieved remission went on to receive HSCT.
Among the full group (N=67), transfusion independence of red blood cells (RBC) and platelets was achieved in 29% and 33% of patients, respectively, who were dependent at baseline. In patients who achieved CR/CRh (n=21), transfusion independence (RBC and platelets) was achieved in 64% (7/11) and 57% (4/7) of patients, respectively, who were dependent at baseline.
The most common Grade 3 or 4 adverse events (≥20% patients) were decreased platelet count (37%), red blood cell count (25%), and neutrophil count (24%). Six patients (9%) experienced differentiation syndrome, of which 2 (3%) were grade 3. Grade 3 or 4 Increases in ALT were reported in 1 patient, AST in 1, ALP in 1, and transaminases in 1. Four patients (6%) discontinued treatment due to an adverse event.
Conclusion: In the first reported analysis of a combination therapy with an mIDH1 inhibitor and an HMA focused on the relapsed/refractory AML setting, olutasidenib plus azacitidine induced high response rates and durable remissions with a tolerable side effect profile in patients with R/R mIDH1 AML.
Disclosures: Cortes: Biopath Holdings: Consultancy, Current holder of stock options in a privately-held company, Membership on an entity's Board of Directors or advisory committees; Nerviano: Consultancy; Ascentage: Research Funding; AbbVie: Research Funding; Syndax: Consultancy; Rigel: Consultancy; Sun Pharma: Consultancy, Research Funding; Pfizer: Consultancy; Novartis: Consultancy, Research Funding; Lilly: Consultancy. Roboz: OncoPrecision: Current holder of stock options in a privately-held company, Honoraria; AbbVie, Amgen, Astrazeneca, Caribou Biosciences, Celgene, Daiichi Sankyo, Ellipses pharma, Geron, GSK, Glycomimetics, Janssen, Jasper Pharmaceuticals, Jazz Pharmaceuticals, Molecular Partners, Oncoverity: Consultancy; Janssen: Research Funding; Novartis, Pfizer, Roche, GlaxoSmithKline, BMS, Syndax, Rigel: Consultancy. Watts: Aptose: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Research Funding; Immune Systems Key: Research Funding; Rafael Pharma: Consultancy; Reven Pharma: Consultancy; Daiichi Sankyo: Consultancy; Incyte: Research Funding; Celgene/BMS: Consultancy; Servier: Consultancy, Membership on an entity's Board of Directors or advisory committees; Rigel: Consultancy, Other: safety monitoring or advisory boards, Research Funding. Jonas: AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Daiichi-Sankyo: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech/Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; GlycoMimetics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Kymera: 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; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Rigel: Consultancy, Other: Travel; Amgen: Research Funding; AROG: Research Funding; Aptose: Research Funding; Celgene: Research Funding; F. Hoffman-La Roche: Research Funding; Forma Therapeutics: Research Funding; Forty-Seven: Research Funding; Hanmi: Research Funding; Immune-Onc: Research Funding; Incyte: Research Funding; Jazz: Research Funding; Loxo Oncology: Research Funding; Pharmacyclics: Research Funding; Sigma Tau: Research Funding; Treadwell: Research Funding. Yee: Astex: Other: research support; Forma Therapeutics: Other: research support; F. Hoffmann-La Roche: Other: research support; Genentech: Other: research support; Geron: Other: research support; Gilead Sciences: Other: research support; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: research support; Bristol Myers Squibb/Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Membership on an entity's Board of Directors or advisory committees; Jazz: Membership on an entity's Board of Directors or advisory committees; Shattuck Labs: Membership on an entity's Board of Directors or advisory committees; Taiho Pharma: Membership on an entity's Board of Directors or advisory committees; Taiho Pharma: Honoraria. Ferrell: Novartis: Research Funding. Yang: Novartis: Consultancy, Research Funding; Puretech: Research Funding; Pfizer: Research Funding. Wang: Immunogen: Membership on an entity's Board of Directors or advisory committees; UptoDate: Other: Section Editor; Jazz: Consultancy, Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Membership on an entity's Board of Directors or advisory committees; Sumitomo Pharma: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; GSK: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sellas: Membership on an entity's Board of Directors or advisory committees; Stemline: Membership on an entity's Board of Directors or advisory committees; NuProbe: Consultancy, Membership on an entity's Board of Directors or advisory committees; CTI Biopharma: Membership on an entity's Board of Directors or advisory committees; Astellas: Consultancy, Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees; Dava Oncology: Speakers Bureau; Qiagen: 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; Syndax: Membership on an entity's Board of Directors or advisory committees; PharmaEssentia: Consultancy, Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo: 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; Kura: Speakers Bureau; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Mana: Membership on an entity's Board of Directors or advisory committees; J&J: Membership on an entity's Board of Directors or advisory committees; Blueprint: Membership on an entity's Board of Directors or advisory committees; Takeda: 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. Mims: BMS: Membership on an entity's Board of Directors or advisory committees; Leukemia and Lymphoma Society Beat AML Study: Other: Senior Medical Director; Daiichi Saynko: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Foghorn Therapeutics: Membership on an entity's Board of Directors or advisory committees; Treadwell Therapeutics: Membership on an entity's Board of Directors or advisory committees.
OffLabel Disclosure: Olutasidenib, approved as a monotherapy
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