Infectious events in fit patients with relapsed or refractory acute myeloid leukemia treated with azacitidine-venetoclax or intensive chemotherapy.

[OBJECTIVES] Second-line therapy for relapsed or refractory acute myeloid leukemia (R/R AML) involves either intensive chemotherapy (ICT) or azacitidine and venetoclax (AZAVEN), but their comparative infectious risks are not well established.

[METHODS] This retrospective multicenter study evaluated infectious events in 246 adult R/R AML patients eligible for allogeneic hematopoietic stem-cell transplantation (HSCT) across five French centers from 2015 to 2023.

[RESULTS] Of these, 163 received ICT and 83 received AZAVEN, with similar baseline characteristics except for more frequent antifungal prophylaxis in the AZAVEN group (55% vs 28%). A total of 358 infectious events were documented, predominantly during hospitalization (90%). Most infections were severe (grade 3 or 4), with no significant difference in fatal infections between groups. Bloodstream infections without organ involvement (38%) and bacterial infections (49%) were most common. By day 100, the cumulative incidence of a first infection was significantly lower with AZAVEN (37%, 95% CI: 26%-47%) than on ICT (82%, 95% CI: 76%-87%), compared to ICT (HR = 0.23, P < 0.001), confirmed by multivariate analysis. Leukemia control rates were similar between groups.

[CONCLUSION] These results suggest that AZAVEN is associated with lower infectious burden than ICT, while maintaining equivalent anti-leukemic efficacy, supporting its use as a bridging therapy before HSCT in fit R/R AML patients.