‘Superior’ Post-HSCT Outcomes with Venetoclax-Containing Triplet in AML

Older patients with acute myeloid leukemia (AML) who underwent allogeneic hemopoietic stem cell transplantation (HSCT) after receiving cladribine and low-dose cytarabine plus venetoclax had “significantly improved survival” compared with those who received other therapies, according to a recent study.

Jayastu Senapati, MBBS, MD, of the University of Texas MD Anderson Cancer Center, and colleagues presented results from the study during the 2023 American Society of Clinical Oncology Annual Meeting.

They compared outcomes between two cohorts of patients. One cohort included 35 patients aged 60 years or older who received treatment in a phase II study of cladribine and low-dose cytarabine plus venetoclax and underwent allogeneic HSCT in their first complete remission (CR). They evaluated the second cohort of patients retrospectively. That cohort included those who were aged 60 years or older and received hypomethylating agent (HMA) venetoclax-based therapy (n=40) or intensive therapy (n=42) and underwent allogeneic HSCT in their first CR between 2013 and 2022.

The median patient age was 68 years in both low-intensity treatment arms and was 62 years in the intensive therapy arm. The median follow-up time was more than 17 months in patients receiving cladribine and low-dose cytarabine plus venetoclax. The median follow-up was 59 months in those receiving intensive therapy, and 30 months in those receiving HMA therapy.

Dr. Senapati and colleagues defined relapse-free survival (RFS) as the time from response to relapse or death and defined overall survival (OS) as the time from the beginning of therapy to death.

The median RFS was not reached in patients receiving cladribine and low-dose cytarabine plus venetoclax, while it was 50 months in those receiving intensive therapy, and 20 months in those receiving HMA therapy (P<.01). The median OS was not reached in patients receiving cladribine and low-dose cytarabine plus venetoclax, while it was 58 months in those receiving intensive therapy, and 32 months in those receiving HMA therapy (P<.01).

The three-year cumulative incidence of relapse was 4% in those receiving cladribine and low-dose cytarabine plus venetoclax, significantly lower than the rate of 17% in patients receiving intensive therapy and the rate of 41% in those receiving HMA therapy. The three-year nonrelapse mortality (NRM) rate was 7% in those receiving cladribine and low-dose cytarabine plus venetoclax, significantly lower than the rate of 23% in patients receiving intensive therapy and the rate of 27% in those receiving HMA therapy.

Older patients with AML who proceeded to HSCT after the triplet therapy had “significantly improved survival characterized by significantly lower rates of NRM and relapse” compared with those who received the two other therapies, Dr. Senapati and colleagues concluded. However, they noted that “larger studies and longer follow-up” of the triplet will be needed to confirm its benefit.

Reference

Senapati J, Kantarjian HM, Bazinet A, et al. Superior outcomes after allogeneic stem cell transplantation (SCT) among patients (pts) ≥ 60 years (yrs) treated with cladribine (CLAD), low dose cytarabine (LDAC) plus venetoclax (ven) for newly diagnosed acute myeloid leukemia (AML). Abstract 7047. Presented at the 2023 American Society of Clinical Oncology Annual Meeting; June 2-6, 2023; Chicago, Illinois.