Intentional Azole Antifungals With Azacitidine-Venetoclax Based Combination In Aml As An Outpatient Therapy: Experience From A Resource-Limited Setting In India

Introduction: Acute myeloid leukemia (AML) primarily warrants intensive induction therapy, followed by consolidation chemotherapy as a curative regimen. However, in elderly (>60 years) and unfit younger patients, less-intense regimens with targeted therapy have been effective. They have proven to be effective regimens for improving overall survival and remission rates while the world battles COVID-19. Patients and Methods: A retrospective study, where case files for all patients diagnosed with AML at a tertiary care center from 2016–2021 were reviewed. The study included patients who received a low-intensity regimen for remission induction, either in upfront or relapsed settings. The primary outcome was complete remission (CR) rates. Results: The median age of the study cohort (n=55) was 45 years (range: 17–75 years), with >60 years comprising 29%; 44.4% had baseline ECOG performance status of >3, which declined to 16.6% after completion of four cycles. The most commonly encountered subtypes were M2 (42.5%) and AML-not otherwise specified (46.3%), according to FAB and WHO classifications, respectively. Azacitidine was employed in 52.7%, azacitidine and venetoclax (aza-ven) in 32.7%, and low-dose cytarabine in 14.5%. In the aza-ven cohort, patients received itraconazole (n=14/18, 77.7%) and voriconazole (n= 4/18, 22.2%) as azoles. The dose of venetoclax varied from 100 to 200 mg and no ramp-up was used. No patients developed TLS. Patients were initiated with remission induction in an outpatient setting. The complete remission rates (CR+CRi) in the aza-ven cohort were 16.6% and 27.7% in treatment-naive and relapsed/refractory settings, respectively. The time to neutrophil and platelet recovery in those achieving CR were 84 days (range: 28–140 days) and 28 days (range: 28–60 days), respectively. The incidence of febrile neutropenia and fungal infection (probable/possible/proven) were 16.6% and 16%, respectively. In the maintenance cohort, azacitidine was primarily used. Interestingly, MRD+ patients (3/10) attained MRD negativity after two cycles, accounting for 100% remission status (10/10). It bridged the gap, allowing three previously unfit patients to receive intensive chemotherapy and two to receive haploidentical transplants. Conclusion: This retrospective study highlights the importance of low-intensity therapy, especially during COVID-19. Aza-ven-azole is a safe and feasible remission induction regimen in patients who are ineligible for intensive induction.