EHA 2018: Alvocidib in Patients With Relapsed or Refractory MCL-1–Dependent AML
Preliminary data from Zella 201—an ongoing phase II study evaluating the efficacy and safety of alvocidib, a potent cyclin-dependent kinase 9 (CDK9) inhibitor, in combination with cytarabine and mitoxantrone in patients with relapsed or refractory MCL-1–dependent acute myeloid leukemia (AML)—were presented by Zeidner et al at the 23rd Annual Congress of the European Hematology Association (EHA) (Abstract PF243).
Findings
Preliminary data from phase I of the study indicated alvocidib in combination with cytarabine and mitoxantrone has shown encouraging activity in 18 patients with MCL-1–dependent AML, with the majority of patients achieving a complete remission (CR) or complete remission with incomplete recovery (CRi). The study found an overall CR/CRi rate of 61% (n = 11) and an overall response rate (ORR, CR/CRi/PR) of 67% (n = 12). In patients who were refractory to frontline therapy, CR/CRi rate was 75% (n = 6) and ORR was 88% (n = 7). Patients that attained a CR/CRi (n = 11) experienced a median duration of response of 8.2 months and median overall survival of 10.1 months. In addition, 44% (n = 8) of patients proceeded to poststudy stem cell transplant, including 63% (n = 5) of previously refractory patients. Adverse events in the study are consistent with those noted in previous studies and include tumor lysis syndrome, sepsis, diarrhea, and elevated AST levels.
“Our understanding of AML is evolving as we deepen our knowledge about the different mechanisms that play a role in the disease,” said Joshua F. Zeidner, MD, lead investigator of the Zella 201 study and Assistant Professor, Lineberger Comprehensive Cancer Center at the University of North Carolina at Chapel Hill. “These preliminary results are encouraging as they indicate alvocidib in combination with cytarabine and mitoxantrone may have activity in patients with relapsed and refractory MCL-1–dependent AML.”
In the study, a total of 21 patients have been enrolled to date, all of whom have MCL-1 dependency of 40% or higher. To date, 18 patients have been evaluated and 3 patients are pending evaluation. Following the completion of the first stage of the study, the study will move to stage 2, a randomized phase II expansion comparing the combination of alvocidib, cytarabine, and mitoxantrone to cytarabine and mitoxantrone.
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