PROMISING results from a recent Phase II clinical trial on the use of vitamin C supplementation for the treatment of low-risk myeloid malignancies were presented at the 2024 European Haematology Association Congress. Patients with haematological cancers are often deficient for the epigenetic regulator TET2, for which vitamin C acts as a cofactor. Therefore, researchers assessed the potential therapeutic benefits and safety of vitamin C supplementation in patients with low-risk myelodysplastic syndromes (MDS), MDS/myeloproliferative neoplasms (MDS/MPN), and clonal cytopenia of undetermined significance (CCUS).
The EVI-2 clinical trial was a randomized, placebo-controlled study between 2017 and 2022. The study comprised 109 patients across four Denmark and the United States centres. Participants were randomized to receive either 1000 mg/day of oral vitamin C or a placebo for 12 months. The primary endpoint was the change in variant allele frequency of somatic mutations in bone marrow mononuclear cells, with secondary endpoints including changes in plasma vitamin C concentration, number of serious adverse events (SAEs), and overall survival (OS).
Baseline data indicated that 57% of the study population had inadequate vitamin C levels (<50 μmol/L). The vitamin C group significantly increased median plasma vitamin C concentration from 45.85 μmol/L at baseline to 81.90 μmol/L at 12 months (P<1×10^-7). Conversely, no significant changes were observed in the placebo group (43.75 μmol/L at baseline and 48.73 μmol/L at 12 months; P=0.92). The authors noted significantly improved OS in participants receiving vitamin C (hazard ratio [HR], 0.35; p= .0025). At the end of the study, with a median follow-up of 33.5 months, 11 deaths had occurred in the vitamin C group compared to 24 in the placebo group. The safety profile of vitamin C supplementation was favourable, with only 27% of patients in the vitamin C group experiencing SAEs compared to 43% in the placebo group.
These findings suggest that vitamin C supplementation not only improves vitamin C plasma levels but also has a significant impact on survival outcomes in patients with low-risk myeloid malignancies. The results warrant further investigation in a larger, better-powered phase 3 study to confirm these benefits and establish vitamin C as a standard adjunct therapy and intervention in this patient population. Study author Stine Ulrik Mikkelsen of Rigshospitalet in Copenhagen, Denmark, concluded that this “largely untoxic, readily available, and inexpensive treatment could represent an attractive therapeutic approach in this category of patients who currently have limited treatment options,”.
Reference
Mikkelsen SU et al. Vitamin C supplementation in patients with clonal cytopenia of undetermined significance or low-risk myeloid malignancies: results from EVI-2, a randomized, placebo-controlled phase 2 study. Abstract LB3444. EHA Annual Congress 13-16 June 2024.
