Peri-Transplant Venetoclax-Based Maintenance Therapy ‘Encouraging’ in MDS, AML

Venetoclax plus azacitidine maintenance therapy after allogeneic hematopoietic stem cell transplantation (HSCT) had “encouraging activity” in patients with high-risk myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML), according to a recent study.

Jacqueline S. Garcia, MD, of the Dana-Farber Cancer Institute, and colleagues presented the results at the 2022 American Society of Hematology Annual Meeting.

They conducted the study to assess the safety and activity of maintenance therapy with venetoclax plus azacitidine after reduced intensity conditioning with venetoclax plus fludarabine and busulfan for allogeneic HSCT.

The 27 patients in the phase I study received reduced intensity conditioning with venetoclax plus fludarabine and busulfan for allogeneic HSCT, with 22 of the 27 receiving maintenance therapy with venetoclax plus azacitidine. The remaining five patients did not receive maintenance therapy due to early relapse or study withdrawal.

The one-year progression-free survival rate (PFS) was 65% (95% CI, 40-82), while the one-year overall survival rate (OS) was 79% in the patients who received maintenance therapy.

In all patients, regardless of maintenance status, the one-year PFS rate was 57% and the one-year OS rate was 70%. The one-year relapse rate in all patients was 43% (95% CI, 28-57), while the one-year non-relapse mortality rate was 0%.

Pre-transplant minimal residual disease (MRD) negativity as measured by flow cytometry was associated with improved one-year OS, with a rate of 88% in patients who had pre-transplant MRD negativity, as opposed to a rate of 50% in those who did not (P=.03). The same was true of one-year PFS rates, with a rate of 81% in those who had pre-transplant MRD negativity as opposed to a rate of 39% in those who did not. (P=.08).

At day 28, 17% of patients were MRD positive, while 44% were MRD positive at day 100. At the time that patients underwent allogeneic HSCT, 89% of patients were positive on a next-generation sequencing assay, reducing to 42% at day 28 and to 58% at day 100.

The researchers did not report any dose-limiting toxicities. The most common grade 3 or grade 4 treatment-emergent adverse event during maintenance was neutropenia, reported in 95% of patients. Thrombocytopenia occurred in 91% and anemia occurred in 45%. The cumulative incidence of grade 2 or higher acute graft-versus-host disease (GVHD) was 22%, while the one-year cumulative incidence of chronic GVHD was 23%.

“[Venetoclax plus azacitidine] maintenance therapy after [reduced intensity conditioning with venetoclax plus fludarabine and busulfan for allogeneic HSCT], appears to be safe with low infection rate and no excessive GVHD,” Dr. Garcia and colleagues concluded. “This [venetoclax]-based peri-transplant strategy for high-risk [patients with] MDS/AML has encouraging activity though relapses still occurred. A cohort assessing all oral maintenance (venetoclax plus decitabine/cedazuridine) is enrolling. A randomized trial will be required to evaluate the benefit of [venetoclax] with conditioning chemotherapy or with maintenance therapy.”

Reference

Garcia JS, Kim HT, Brock J, et al. Maintenance therapy with venetoclax/azacitidine can be safely given after venetoclax/FluBu2 RIC allogeneic transplantation for the treatment of high risk MDS/AML: results of a phase 1 study. Abstract #377. Presented at the 64th ASH Annual Meeting and Exposition; December 10-13, 2022; New Orleans, Louisiana.