Approximately one-quarter of patients with high-risk myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML) who received venetoclax plus azacitidine maintenance therapy after allogeneic hematopoietic stem cell transplantation (HSCT) developed chronic graft-versus-host disease (GVHD).
Jacqueline S. Garcia, MD, of the Dana-Farber Cancer Institute, and colleagues presented the results at the 64th American Society of Hematology Annual Meeting and Exposition.
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 5 patients did not receive maintenance therapy due to early relapse or study withdrawal.
The 1-year progression-free survival rate (PFS) was 65% (95% CI, 40-82), and the 1-year overall survival rate (OS) was 79% in the patients who received maintenance therapy.
In all patients, regardless of maintenance status, the 1-year PFS rate was 57% and the 1-year OS rate was 70%. The 1-year relapse rate in all patients was 43% (95% CI, 28-57), whereas the 1-year nonrelapse mortality rate was 0%.
Pretransplant minimal residual disease (MRD) negativity as measured by flow cytometry was associated with improved 1-year OS, with a rate of 88% in patients who had pretransplant MRD negativity, as opposed to a rate of 50% in those who did not (P=.03). The same was true of 1-year PFS rates, with a rate of 81% in those who had pretransplant MRD negativity and a rate of 39% in those who did not. (P=.08).
At day 28, 17% of patients were MRD positive, whereas 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 III-IV treatment-emergent adverse event during maintenance was neutropenia, reported in 95% of patients. Thrombocytopenia occurred in 91% patients and anemia occurred in 45%. The cumulative incidence of grade II or higher acute GVHD was 22%, and the 1-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.”
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.