Safety and efficacy of Vitamin D(3) supplementation with Imatinib in Chronic Phase- Chronic Myeloid Leukaemia: an Exploratory Randomized Controlled Trial

OBJECTIVES: The study aimed to compare early molecular response (EMR) rates at 3 months of imatinib therapy with and without vitamin D(3) supplementation in patients newly diagnosed with chronic-phase chronic myeloid leukaemia (CML-CP). The secondary objective was to assess the effects of vitamin D(3) on complete haematological response (CHR) and its safety. DESIGN: Double-blind, placebo-controlled, exploratory randomised trial. SETTING: Tertiary care hospital in northern India. PARTICIPANTS: Treatment-naive patients with chronic phase chronic myeloid leukaemia (n=62) aged >12 years were recruited from January 2020 to January 2021. Patients with progressive disease, pregnancy and hypercalcaemia were excluded. INTERVENTION: Oral vitamin D(3) supplementation (60 000 IU) or matched placebo was given once weekly for an initial 8 weeks along with imatinib after randomisation with 1:1 allocation ratio. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was to compare EMR (defined as BCR-ABL1 transcript level ≤10%, international scale) at 3 months. The secondary outcomes were to compare effect of the intervention on CHR, correlation of 25(OH)2D(3) levels with treatment response and safety according to Common Terminology Criteria for Adverse Events (CTCAE) version 5. RESULTS: At baseline, 14.5% of the patients had normal vitamin D(3) levels. EMR at 3 months was attained in 24 patients (82.7%) of the vitamin D(3) group and 21 (75%) of the placebo group (OR 1.6, 95% CI 0.37 to 7.37, p=0.4). A significant difference in vitamin D(3) levels from baseline to the end of study was observed. Patients with vitamin D(3) supplementation did not achieve higher CHR in comparison with placebo (OR 1.3, 95% CI 0.25 to 7.23, p=1.0). Vitamin D3 levels were not significantly correlated with BCR-ABL1 levels. No dose-limiting toxicities were observed. CONCLUSION: Vitamin D(3) levels were low among patients with CML-CP in this study. Vitamin D(3) supplementation with imatinib therapy did not have significant effect on EMR or CHR. Further clinical trials could be undertaken to assess the effective dosage and duration of vitamin D(3) supplementation in these patients. TRIAL REGISTRATION NUMBER: CTRI/2019/09/021164.