Frontline HMA Plus Venetoclax May Improve Outcomes in Secondary AML

Treatment with a hypomethylating agent plus venetoclax followed by hematopoietic stem cell transplant could improve outcomes in patients with treated secondary acute myeloid leukemia.

Patients with treated secondary acute myeloid leukemia (ts-AML) who undergo treatment with a hypomethylating agent (HMA) plus venetoclax (Venclexta) followed by hematopoietic stem cell transplantation (HSCT) could experience improved outcomes, especially those with a non-adverse risk karyotype, according to a study published in the Journal of Hematology & Oncology.

Treatment with HMA plus venetoclax resulted in a complete remission (CR)/incomplete hematologic recovery (CRi) rate of 39% compared with 25% for intensive chemotherapy or low-intensity therapy without venetoclax (P = .02). The overall survival (OS) at 1-year was 34% and 17% (P = .05) in the HMA plus venetoclax and intensive/low-intensity chemotherapy groups, respectively.

A total of 562 patients enrolled and received frontline treatment, 271 of whom received intensive chemotherapy, 237 received low-intensity therapy without venetoclax, and 54 received HMA plus venetoclax. The median patient age was 69 years, and the median number of prior therapies received for antecedent hematologic malignancies was 1. Moreover, 41% of patients received 2 or more therapies prior to being diagnosed with AML. Prior allogeneic HSCT was used in 10% of patients for myelodysplastic syndrome or chronic myelomonocytic leukemia.

In the overall population, the CR rate was 16% and the CR/CRi rate was 26%. Investigators reported a 30-day mortality rate of 9% and a 60-day mortality rate of 14%. The median duration of follow-up was 47 months, and the median duration of response was 7.7 months. Additionally, the median relapse-free survival (RFS) was 5.7 months and the RFS rate at 1-year was 26% and at 2-years it was 17%. The median OS was 4.8 months and the 1- and 2-year OS rates were 19% and 7%, respectively.

The CR/CRi/morphologic leukemia–free state rate was higher with HMA plus venetoclax group at 54% vs 32% in the intensive chemotherapy group and low-intensity therapy without venetoclax cohort (P = .002). Treatment with HMA plus venetoclax in those who had a non-adverse karyotype yielded CR/CRi rate of 57% compared with 30% in the control group (P = .008). Regardless of treatment approach, those with ts-AML and an adverse karyotype had a CR/CRi rate of 18% and 16%, respectively (P = .8).

Those who received HMA plus venetoclax had a 30-day mortality rate of 10%, with those having intensive chemotherapy, 9% with low-intense therapy, and 7% with HMA plus venetoclax (P = .74) compared with the 60-day mortality rates of 25%, 22%, and 20%, respectively (P = .71).

The median RFS was 12.9 months in the HMA plus venetoclax group compared with 5.3 months in the intensive and low-intensity therapy group. The 1-year OS was 55% in the HMA group and 22% in the intensive chemotherapy/low-intensity therapy group (P = .04).

A subgroup analysis found that patients who were 60 years or older had a notable OS benefit when treated with HMA plus venetoclax compared with intensive chemotherapy. The median OS was 5.8 months in the experimental arm vs 4.1 months in the control arm. The 1-year overall response rate was 35% vs 12% in both respective arms (P = .009). Additionally, patients with adverse risk karyotypes had a median OS of 3.5 months for the intensive chemotherapy groups and 3.2 months for the HMA plus venetoclax group (P = .88). The superior OS gained through treatment with the experimental combination was exclusive to those with non-adverse risk karyotype.

Reference

Short NJ, Venugopal S, Qiao W, et al. Impact of frontline treatment approach on outcomes in patients with secondary AML with prior hypomethylating agent exposure. J Hematol Oncol. 2022;15(1):12. doi:10.1186/s13045-022-01229-z