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Oral Prednisolone, Etoposide, 6- Mercaptopurine (PREM) metronomic chemotherapy in treatment naïve and partially treated acute myeloid leukemia in a resource constrained setting

Background: Standard 3 + 7 induction (anthracycline + cytarabine) and consolidation high-dose cytarabine are toxic, expensive, and resource intensive. Objectives: The objective was to evaluate response rates and survival with PRednisolone, Etoposide and 6-Mercaptopurine (PREM) metronomic chemotherapy in treatment-naïve, and partially treated acute myeloid leukemia (AML). Materials and Methods: All patients with AML, registered between June 01, 2017, and May 31, 2019, not willing for standard 3 + 7 induction (Group A) due to financial constraints and those who refused to complete at least two cycles of cytarabine consolidation (Group B) and received oral PREM therapy were analyzed. Bone marrow aspiration/biopsy was used for response evaluation in the 3rd month in Group A. Descriptive statistics and survival according to the Kaplan-Meier method were used to evaluate outcomes with SPSS v. 17. The follow-up was calculated using reverse Kaplan–Meier method. Results: Fifteen patients were included in the study, 11 in Group A and 4 in Group B. The median follow-up was 13 months in Group A (range, 10–14 months). 5/11 (46%) and 2/11 (18%) achieved complete response (CR) and partial response (PR), respectively. The 1-year survival of patients in Group A (n = 11) was 45% with a median overall survival of 9 months (95% confidence interval [CI], 5.4–11.6 months). Among the 7 out of 11 patients (64%) who responded (CR + PR), the 1-year survival was 70% with a median survival of 12 months, versus 3 months for patients who failed to attain a response, P = 0.005 with hazard ratio of 0.05 (95% CI, 0.01–65.65). In the patients in Group B (n = 4), all patients sustained/achieved CR and were alive without relapse at a median follow-up of 24.5 months (range, 22–26 months). The ratio of total inpatient admissions in Group A patients (n = 11) was 1.7 in the first 3 months with median duration of 7 days (range, 4–14 days). Conclusion: Oral PREM metronomic chemotherapy led to favorable responses in treatment naive AML patients. The regimen also led to sustained remissions in patients with partially treated AML.