A prospective observational study to compare the efficacy, time toxicity, and cost of conventional 3+7 regimen versus azacitidine + venetoclax (AZA + VEN) as induction therapy in patients with acute myeloid leukemia (AML).

6511 Background: In low-middle income countries, 3+7 induction therapy for AML is associated with high induction mortality (7-40%), more so in patients with infections at diagnosis. Given the activity of AZA+VEN, a considerable proportion of patients with high-risk features (infections at diagnosis, poor-risk AML, poor performance status, multiple comorbidities, elderly) or long-waiting for admission to start induction are treated with AZA+VEN and 3+7 regimen use is limited to young, fit and good/intermediate risk groups. However, it is important to understand if use of AZA+VEN in this setting provides similar efficacy and is safe without increasing the cost of therapy and time-toxicity as defined by the contact days with healthcare system. Ideally a randomized controlled trial is needed to answer this question, however physicians’ unwillingness to randomize patients at high-risk of induction mortality to 3+7 regimen would challenge the feasibility of such trial. Methods: A prospective observational study enrolled consecutive de-novo AML patients aged ≥18-years after written informed consent who were planned for treatment by a multi-disciplinary joint clinic with either 3+7 or AZA+VEN. The primary endpoint was induction mortality, with secondary endpoints of grade 3/4 toxicity, treatment cost, time toxicity, complete response/complete response rate with incomplete count recovery rates (CR/CRi) assessed after one course. Results: 154 participants were included (3+7 -73, AZA+VEN-83). Median age was 35 years in 3+7 as compared to 44 years in Aza-Ven group. The AZA+VEN group was enriched for high-risk features – ECOG PS ≥2 (10.9% vs 33.3%), baseline fungal pneumonia (4.1% vs 50%), poor-risk profile as per ELN 2022(12.3% vs 24.7%). The primary reasons for starting AZA+VEN were active infection (65.4%), poor-risk disease (28.4%), delay in admission (16%), and poor performance status (8.6%). Induction mortality was comparable between 3+7 and AZA+VEN (8.2% vs 7.5%). Toxicities were higher with 3+7; febrile neutropenia (95.9% vs 79.7%), new-onset bacterial infections (49.3% vs 19.0%) with multidrug resistant bacterial sepsis (32.9% vs 9.1%), and new-onset fungal pneumonia (27.4% vs 15.2%). The median treatment cost was higher with 3+7 (227,790 INR) compared to AZA+VEN (184,694 INR). Time toxicity (26.0±0.8 vs 19.0±0.9 days) and duration of hospitalization (26.0±0.9 vs 18.0±2.1 days) were higher in the 3+7. CR/CRi rates were higher with 3+7 (80.6% vs 57.1%), including higher CR (52.2% vs 27.1%) and flow-MRD negativity (71.6% vs 41.9%) driven by the favorable risk profile in this group. Conclusions: The study demonstrated that AZA+VEN in patients who are at high-risk of induction mortality provides a valuable alternative with better safety and reduced financial burden and time toxicity.