Acute Myeloid Leukemia is a common hematological malignancy of myeloid origin. 

According to the ELN (European Leukemia Net) patients with AML are stratified based on cytogenetics and molecular abnormalities into good, intermediate and poor risk groups.

Treatment of AML is divided into an induction and post-remission therapy phase. The induction phase consists of aggressive chemotherapy regimens designed to eradicate the bone marrow of the neoplastic cells and induce a complete remission (CR). Once CR is achieved, post-remission therapy (consolidation chemotherapy or allogeneic stem cell transplant) is needed to prevent relapse. According to the risk group and mininimal residual disease, patients are considered for allogeneic stem cell transplant based on the availability of HLA-matched donor.

However, there are many challenges to delivering the conventional induction chemotherapy (IC) with 3 + 7 regimen with daunomycin and cytarabine. Patients with poor ECOG performance status, elderly patients and those with life-threatening infections are usually not able to tolerate IC regimen and succumb during induction. The induction related mortality in clinical trials and real-world data is approximately 5 percent. However, studies from developing countries like India reveal that the figure is about 10 to 25 percent.  The reasons for this are high prevalence of multi-drug resistant organisms, late presentation to the hospital, presence of infections at diagnosis, and delayed initiation of treatment. In addition, the need for supportive care, broad-spectrum antibiotics, antifungals, intensive care admissions and prolonged hospitalization adds significant financial burden on the patients and accentuates resource constraints in health care systems resulting in further treatment abandonment, delays and inefficient delivery of care.

Hence we are in need of a regimen that can be delivered largely on an outpatient basis, has lower induction mortality and other toxicities requiring hospitalization and does not impose excessive financial burden on the patient and the family. Azacitidine and Venetoclax based induction may be able to address some of these challenges of conventional IC.

Based on the data on activity of AZA + VEN, relatively better toxicity profile, and long waiting period for IC due to non-availability of beds, many of our patients are given Azacitidine and Venetoclax if they meet any of the following criteria

Poor risk AML

Elderly patients above the age of 60

Good and intermediate risk patients with poor ECOG PS (more than 2)

Good and intermediate risk patients with serious infections who are at high-risk of induction related mortality with IC

There is a limited data at present comparing the two regimens, IC and AZA +VEN. Hence we want to conduct this study in order to objectively assess if AZA + VEN can truly reduce the mortality, complications, hospitalizations and cost compared to IC, while at the same time not compromise induction outcomes. The ideal way to answer this question would be to conduct a randomized clinical trial to compare the two regimens. However, a prospective observational study would be able to provide an indication on the efficacy and toxicity of the two regimens as the subset receiving AZA+VEN would be enriched with high-risk patients both due to underlying disease (poor-risk), age and presence of infections.

Such a study can be a forerunner for larger, multicenter studies to address the important question of which regimen is effective and less toxic at the same time.

Hence we propose a study to prospectively compare these two regimens in terms of toxicity and outcomes.