Results of a phase 2 sub-study of the Beat AML Master Trial were shared at the 2021 American Society of Hematology (ASH) Annual Meeting to discuss poor response and survival rates associated with entospletinib and decitabine as a treatment combination for older patients with newly diagnosed acute myeloid leukemia (AML).

“Novel treatment strategies that can benefit patients with AML who have the most adverse risk factors are urgently needed. Patients with AML and TP53 mutations are commonly associated with older age and complex karyotype (CK). They experience poor responses to standard 7+3 induction chemotherapy overall with less than 10 percent 1-year overall survival (OS),” explained Vu Duong, MD, University of Maryland Greenbaum Cancer Center, Baltimore, and co-researchers.

The multicenter (13 sites), open-label, phase 2 study enrolled 45 patients with AML and a TP53 mutation plus CK to cohort A and 13 patients with CK (≥3 metaphase abnormalities) without a TP53 to cohort B, respectively.

The primary endpoint was composite complete remission (CCR) with up to 3 cycles of induction and complete remission with incomplete hematological recovery/morphological leukemia-free state (CRi/MLFS) that achieved complete response/partial hematologic response (CR/CRh) by up to 6 cycles of induction plus consolidation.

“During lead-in, 27 patients in cohort A and 6 patients in cohort B received entospletinib for 5 days. All patients received entospletinib plus decitabine except 1 patient in cohort A who withdrew consent (WOC),” said Dr Duong and co-authors.

The median age of patients in cohort A was 70 (range, 60-84) and 74 years (range, 65-86) in cohort B. The median time of treatment was 2.2 and 4.8 months in cohort A and B, respectively.

Notably, the most common reasons for treatment discontinuation in cohort A were adverse events (AEs; 27%), treatment failure (TF; 27%), and WOC (18%). In cohort B the most common reasons were TF (31%), disease progression and relapse (each 15%). In each cohort, 1 patient discontinued treatment due to death from leukemia and 1 patient in cohort A in CRh due to the development of an additional genetic abnormality.

“The CCR rates with up to 6 cycles of treatment for cohort A and B were 13.3 percent and 30.8 percent, respectively. Overall CR plus CRh rates were 17.8 percent and 38.5 percent,” reported Dr Duong and co-researchers.

In cohort A, with a median follow-up time of 11.5 months, 0 percent were 1-year disease-free and median OS was 6.5 months. In cohort B, with a median follow-up of 15.1 months, 25 percent were 1-year disease-free and the median OS was 11.5 months.

The most common treatment-related adverse events (TEAEs) in cohort A and B were febrile neutropenia (31% and 39%) and anemia (22% and 31%). Overall, 83 serious AEs were reported in 33 patients in cohort A and 12 in cohort B.

“Entospletinib plus decitabine demonstrated activity in newly diagnosed AML in both cohorts but induced low CR/CRh rates and short OS consistent with previously published poor CR rates and OS in this patient population. Our results differ from the high remission rate and longer OS previously reported for decitabine monotherapy in patients with AML and TP53 mutations,” concluded Dr Duong, et al. –Alexa Stoia

Duong V, Ruppert A, Mims A, et al. Entospletinib and Decitabine Combination Therapy in Older Newly Diagnosed Acute Myeloid Leukemia Patients with Mutant TP53 or Complex Karyotype Is Associated with Poor Response and Survival: A Phase 2 Sub-Study of the Beat AML Master Trial. Presented at: the 2021 ASH Annual Meeting; Dec. 11-14; 2021; Abstract 1279.