Individualized AML Induction with Venetoclax Based Therapy in Unfit Treatment Naïve Patients Aged ≤ 60 Years: A Real World Perspective from India

Introduction: Although AML outcomes have reportedly improved in the developed world, outcomes continue to be poor in low middle income countries (LMIC). Apart from financial constraints, presence of baseline infections is one of the major reasons for early mortality and treatment deferral. According to an Indian study of 268 patients acute leukemia, more than 54% patients had baseline infections out of which only 40% received induction versus 93 % patients who did not have baseline infections.(Ragesh R et al EHA23 abstract book: Hemasphere; 2018) Venetoclax has improved outcomes in AML and has been approved in elderly population. There is an unmet need for protocols for younger patients who are unfit for 3+7 due to multi drug resistant baseline infections or ECOG ≥2 or organ dysfunction. Methods: This is a single centre prospective observational study of AML patients who received either Azacytidine+Venetoclax or modified 3+7 regimen with Venetoclax. We recruited 26 AML patients aged 60 or younger who had clinico-radiological evidence of infection or ECOG PS ≥2 or comorbidities from July'19 to March'21. Therapy was individualized based on the nature of infections, ECOG PS and co morbidities into two cohorts by the treating panel. Cohort A (n=12) received Azacytidine @75mg/m 2 x 7 days with Venetoclax 100mg on day1, 200mg on day 2 and 100mg from day 3 with Voriconazole from day 3 onwards as antifungal prophylaxis and to reduce the cost. This regimen was preferred in patients who were unfit to receive modified 3+7 regimen. Cohort B (n=14) received modified 3+7. This included backbone of Cytarabine (Ara C) infusion @100mg/m 2 with Venetoclax. Daunorubicin @60mg/m 2 was added based on the clinical status of the patient.Venetoclax was added from day one in the similar ramp up manner as in cohort A. Day 14 bone marrow examination and cytopenias were used to guide the duration of Venetoclax(range 7-14 days). Daunorubicin doses were individualized as follows: Two doses of Daunorubicin were given to hemodynamically stable patients who showed recovery following antimicrobial therapy. Single dose of Daunorubicin was given to patients with multiple foci of infections or those who required ICU stay either before or during the initiation of therapy. Daunorubicin was omitted in patients on ventilatory support.Ara C infusion was limited to 5 days with 2 doses of Daunorubicin. Patients who achieved CR and had their infections resolved received standard consolidation like Hi