Objectives: Acute myeloid leukemia (AML) patients are at high risk of invasive aspergillosis (IA) and required a mould active antifungal prophylaxis during induction chemotherapy (CHT). Although IA risk factors have been identified, few data are available on impact of IA, occurring during first remission induction phase, on overall AML outcome.
Methods: The primary endpoint of this prospective, multicentric, case-control study, was to evaluate if IA, occurring during first remission-induction CHT, can affect treatment schedule and, consequently, patient overall survival (OS). We identified 40 AML patients (cases) who developed IA during induction phase, 31 probable (67%) and 9 proven (33%) IA. These cases were matched with a control group (80 AML) without IA, balanced according to age, type of induction CHT, AML characteristics and cytogenetic-molecular risk factors. The overall response rate to induction CHT was the same in the 2 groups.
Results: In the 40 cases with AI, the overall response rate (ORR) to antifungal treatment was favorable (ORR 80%) but it was significantly affected by the achievement of leukemia complete remission (CR) with induction CHT. In fact, in cases with AML responsive to induction CHT, complete responses of IA to antifungal therapy were 96% compared to 21% in cases of AML not responsive to induction CHT (p <0.0001). The adherence to schedule and full doses of CHT was reported in 35% of cases (14/40) and in 76% of controls (61/80) (p = 0.0001). After induction CHT a significant higher number of cases (15/40; 37.5%) compared to controls (21/80; 26%) could not receive additional cycles of CHT (p = 0.01). The IFI related mortality was 22.5%. Comparing OS of 40 cases with the OS of the 80 controls, the median OS of cases was significantly worse with a difference of 12.3 months (12.1 vs 24.4 months, p = 0.04-Figure 1A). However, the occurrence of IA during induction phase did not have a significant impact on the OS of cases who achieved a CR with induction CHT which are able to proceed, despite the IA, with their intensive therapeutic program, achieving the same OS as the control group with an AML in CR (p = ns-Figure 1B).
Conclusion: These data showed that IAs during induction CHT can delay the subsequent therapeutic program and has a significant impact on OS of AML, specifically in those patients with IA occurring during induction phase who did not achieved a CR of AML with the first course of CHT (Figure 1C).
Full conference title:
- TIMM (2019)