Session: 616. Acute Myeloid Leukemias: Investigational Therapies, Excluding Transplantation and Cellular Immunotherapies: Poster II
Hematology Disease Topics & Pathways:
Research, clinical trials, Acute Myeloid Malignancies, AML, MDS, Clinical Research, Chronic Myeloid Malignancies, Diseases, Myeloid Malignancies
Methods—This ongoing Phase 2 trial (NCT04827719) enrolled HR MDS and AML patients (pts) aged ≥ 75 years or with comorbidities incompatible with intensive chemotherapy. MDS pts were refractory or had relapsed to azacytidine (AZA), and AML pts to AZA, low-dose cytarabine (LDAC) or AZA -venetoclax (VEN), given as a first line regimen. Each BST-236 induction and maintenance course consisted of 6 daily 1-hour intravenous infusions at a dose of 4.5 g/m2/d (containing 3 g/m2/d of cytarabine). After completing 1 induction cycle, patients with stable disease (SD) or partial response could undergo a second similar cycle, and patients who achieved complete remission (CR) could receive 2 to 4 maintenance cycles at the same schedule. Inclusion of 20 AML and 20 MDS pts was planned.
Results— From August 2021 to May 2023, 16 MDS and 20 AML pts from 9 centers were enrolled, with a median follow up of 3 months.
MDS: Median age was 74.8 years [IQR, 71.2-76.4] and ECOG was 0- 1 in all but 1 patient . All pts were previously treated with AZA and 4 (29%) had adverse R-IPSS karyotype. 14/16 were evaluable for response after 1 induction: 1 (7%) CR, 2 (14%) marrow CR, 7 (50%) SD. Hematological improvement was observed in 6 (43%) patients. Two serious treatment related adverse events (SAE) - febrile neutropenia and sepsis - occurred in 2 pts. Median duration of hospitalization for the induction cycle was 29.5 days [IQR 25.5-32.5] and 30-day mortality rate was 0%.
AML: Median age was 77.6 years [IQR, 73.8-79.4] and all pts had ECOG 0-1. Two pts were previously treated with AZA, 1 with LDAC, 17 with AZA-VEN and 8 (50%) had adverse ELN score. 17/ 20 pts were evaluable for response after 1 induction cycle : 2 (12%) CR including 1 CR with negative MRD, 1 (6%) CRi, 10 (59%) SD. Three SAE- infections and hepatobiliary disorders- occurred in 2 pts. Median duration of hospitalization for the induction cycle was 26 days [IQR 23.2-30.8] and 30-day mortality rate was 10%.
Four MDS pts still need to be enrolled, and follow up is ongoing. An update will be presented at the meeting.
Conclusion— Response rates with BST-236, in this pretreated older frail R/R AML and MDS population, were modest. Toxicity, including myelosuppression, however appears lower than with conventional intensive chemotherapy, suggesting this treatment could be interesting earlier in the disease course.
Disclosures: Cluzeau: Syros: Speakers Bureau; Keros: Speakers Bureau; Servier: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Jazz Pharma: Consultancy, Speakers Bureau; Abbvie: Consultancy, Speakers Bureau; Incyte: Speakers Bureau; BMS: Consultancy, Speakers Bureau. Papayannidis: Abbvie, Astellas, Servier, Menarini/Stemline, BMS, Pfizer, Amgen, Janssen, Incyte, Novartis: Honoraria; Pfizer, Astellas, Janssen, GSK, Blueprint, Jazz Pharmaceuticals, Abbvie, Novartis, Delbert Laboratoires: Membership on an entity's Board of Directors or advisory committees. Fenaux: Janssen: Consultancy, Honoraria, Research Funding; Bristol Myers Squibb: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding; Jazz: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; French MDS Group: Honoraria.