CLAD + LDAC + Ven or Aza + Ven for older or unfit patients with ND AML: Phase II results

Results from a single-center, single-arm phase II study (NCT03586609) evaluating cladribine (CLAD) + low-dose cytarabine (LDAC) + venetoclax (Ven), alternating with azacitidine (Aza) + Ven, in 190 patients with newly diagnosed (ND) acute myeloid leukemia (AML) who were aged ≥60 years or ineligible for intensive chemotherapy were published in the American Journal of Hematology by Kadia et al. The primary objective was composite complete remission (CRc) rate in the first two cycles. Secondary objectives included overall survival (OS), disease-free survival (DFS), overall response rate (ORR), treatment toxicity, and induction mortality.

Key data: The CRc rate was 84%, with 75% of responding patients achieving a measurable residual disease (MRD)-negative complete response (CR)/CR with incomplete blood count recovery (CRi). At a median follow-up of 30 months, the median OS was 52 months; 2- and 5-year OS rates were 60% and 45%, respectively. The median event-free survival (EFS) was 50 months. Among patients achieving a response, the median DFS and duration of response (DoR) were 51 months and 51.5 months, respectively. The mortality rates at 4 and 8 weeks were 1% and 3%, respectively. Grade 3/4 adverse events (AEs) occurred in 47% of patients and most commonly involved infectious complications.

Key learning: CLAD + LDAC + Ven alternating with Aza + Ven is an effective and well-tolerated lower-intensity regimen for patients with ND AML who are older or unfit for intensive chemotherapy.