Safety and efficacy of Vitamin D3supplementation with Imatinib in Chronic Phase- Chronic Myeloid Leukaemia: an Exploratory Randomized Controlled Trial

Abstract

ObjectivesThe study aimed to compare early molecular response (EMR) rates at 3 months of imatinib therapy with and without vitamin D3supplementation in patients newly diagnosed with chronic-phase chronic myeloid leukaemia (CML-CP). The secondary objective was to assess the effects of vitamin D3on complete haematological response (CHR) and its safety.DesignDouble-blind, placebo-controlled, exploratory randomised trial.SettingTertiary care hospital in northern India.ParticipantsTreatment-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.InterventionOral vitamin D3supplementation (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 measuresThe primary outcome was to compare EMR (defined asBCR-ABL1transcript level ≤10%, international scale) at 3 months. The secondary outcomes were to compare effect of the intervention on CHR, correlation of 25(OH)2D3levels with treatment response and safety according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.ResultsAt baseline, 14.5% of the patients had normal vitamin D3levels. EMR at 3 months was attained in 24 patients (82.7%) of the vitamin D3group 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 D3levels from baseline to the end of study was observed. Patients with vitamin D3supplementation 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 withBCR-ABL1levels. No dose-limiting toxicities were observed.ConclusionVitamin D3levels were low among patients with CML-CP in this study. Vitamin D3supplementation 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 D3supplementation in these patients.Trial registration numberCTRI/2019/09/021164.