Entospletinib with decitabine in acute myeloid leukemia with mutant TP53 or complex karyotype: A phase 2 substudy of the Beat AML Master Trial
Year: 2023
Type: article
Abstract: Background Patients with acute myeloid leukemia (AML) who have tumor protein p53 (TP53) mutations or a complex karyotype have a poor prognosis, and hypomethylating agents are often used. The authors evaluated the efficacy of entospletinib, an oral inhibitor of spleen tyrosine kinase, combined with decitabine in this patient population. Methods This was a multicenter, open‐label, phase 2 substudy of the Beat AML Master Trial (ClinicalTrials.gov identifier NCT03013998) using a Simon two‐stage design. Eligible patients aged 60 years or older who had newly diagnosed AML with mutations in TP53 with or without a complex karyotype (cohort A; n = 45) or had a complex karyotype without TP53 mutation (cohort B; n = 13) received entospletinib 400 mg twice daily with decitabine 20 mg/m2 on days 1–10 every 28 days for up to three induction cycles, followed by up to 11 consolidation cycles, in which decitabine was reduced to days 1–5. Entospletinib maintenance was given for up to 2 years. The primary end point was complete remission (CR) and CR with hematologic improvement by up to six cycles of therapy. Results The composite CR rates for cohorts A and B were 13.3% (95% confidence interval, 5.1%–26.8%) and 30.8% (95% confidence interval, 9.1%–61.4%), respectively. The median duration of response was 7.6 and 8.2 months, respectively, and the median overall survival was 6.5 and 11.5 months, respectively. The study was stopped because the futility boundary was crossed in both cohorts. Conclusions The combination of entospletinib and decitabine demonstrated activity and was acceptably tolerated in this patient population; however, the CR rates were low, and overall survival was short. Novel treatment strategies for older patients with TP53 mutations and complex karyotype remain an urgent need.
Source: Cancer
DOI: 10.1002/cncr.34780
Authors: Vu H. Duong, Amy S. Ruppert, Alice S. Mims, Uma Borate, Eytan M. Stein, Maria R. Baer, Wendy Stock, Tibor Kovacsovics, William Blum, Martha L. Arellano, Gary J. Schiller, Rebecca L. Olin, James M. Foran, Mark R. Litzow, Tara L. Lin, Prapti A. Patel, Matthew C. Foster, Robert L. Redner, Zeina Al‐Mansour, Christopher R. Cogle, Ronan T. Swords, Robert H. Collins, Jo‐Anne Vergilio, Nyla A. Heerema, Leonard Rosenberg, Ashley O. Yocum, Sonja Marcus, Timothy Chen, Franchesca Druggan, Mona Stefanos, Theophilus J. Gana, Abigail B. Shoben, Brian J. Druker, Amy Burd, John C. Byrd, Ross L. Levine, Michael M. Boyiadzis
Institutions: University of Maryland, Baltimore, University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, The Ohio State University, Memorial Sloan Kettering Cancer Center, University of Chicago, University of Utah, Huntsman Cancer Institute, Emory University, Winship Cancer Institute, University of California, Los Angeles, University of California, San Francisco, UCSF Helen Diller Family Comprehensive Cancer Center, Mayo Clinic in Florida, Mayo Clinic, University of Kansas Medical Center, The University of Texas Southwestern Medical Center, University of North Carolina at Chapel Hill, UNC Lineberger Comprehensive Cancer Center, UPMC Hillman Cancer Center, University of Pittsburgh Medical Center, University of Florida Health, University of Florida, Oregon Health & Science University, OHSU Knight Cancer Institute, Foundation Medicine (United States), Blood Cancer United, University of Cincinnati
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Funder: National Cancer Institute
OpenAlex ID: W4366462667