Vitamin C supplements tied to improved survival in low-risk myeloid malignancy

Vitamin C deficiency is not uncommon among patients with haematological cancer, but vitamin C supplementation can help address this condition and even provide a survival benefit, suggests a study presented at EHA 2024.

“Vitamin C deficiency was effectively ameliorated in patients receiving oral vitamin C study treatment,” said lead author Dr Stine Ulrik Mikkelsen from Rigshospitalet, Department of Hematology, Copenhagen and the Biotech Research and Innovation Centre, University of Copenhagen, Copenhagen, Denmark.

Mikkelsen and colleagues conducted this randomized, placebo-controlled phase II study to determine if oral vitamin C supplementation was safe and if it could change the molecular and clinical disease characteristics as well as outcomes in patients with low-risk myeloid malignancies (ie, low-risk myelodysplastic neoplasms [MDS; IPSS-R score ≤3] and MDS/myeloproliferative neoplasms) and the precursor condition clonal cytopenia of undetermined significance.

Between 2017 and 2022, 55 patients received oral vitamin C and 54 received placebo at four centres in Denmark (n=3) and the US (n=1). In the vitamin C group, the median age of participants was 72.3 years (range, 46‒87) and 65 percent were males. In the placebo group, the median age was 75.0 percent (range, 58‒87), with 78 percent male patients. [EHA 2024, abstract LB3444]

More than half of the study population (57 percent) had inadequate vitamin C concentration in peripheral blood plasma at baseline (<50 µmol/L). Vitamin C plasma concentration significantly increased in the vitamin C arm from 45.85 µmol/L at baseline to 81.90 µmol/L at 12 months (p<1x10^-7), but changes were not significant in the placebo group, from 43.75 µmol/L at baseline to 48.73 µmol/L at 12 months (p=0.92).

Serious adverse events (SAEs) also occurred more frequently in the placebo group (57 SAEs in 23 of 54 patients, 43 percent) than in the vitamin C group (31 SAEs in 15 of 55 patients, 27 percent).

At the end of the study, 35 deaths were recorded over a median follow-up of 33.5 months (range, 0‒70.0). Interestingly, more patients in the placebo group died compared with those in the vitamin C group (24 vs 11 patients, respectively). The median overall survival was 42.2 months in the placebo arm (HR, 2.88, 95 percent confidence interval, 1.41‒5.89; p=0.0025) and was not reached in the vitamin C arm.

In multivariate analysis, treatment with oral vitamin C still showed a significant association with a longer OS as opposed to treatment with placebo.

“[T]he significantly longer OS observed in the vitamin C group compared to the placebo group warrants further investigation in a sufficiently powered phase III study,” Mikkelsen said.

“Vitamin C is a cofactor for the important epigenetic regulator, TET2, [but] patients with haematological cancer are often vitamin C deficient,” according to Mikkelsen. “Acquired epigenetic changes are a hallmark of myeloid malignancies and TET2 loss-of function mutations are common drivers of leukemogenesis; [t]hus, vitamin C supplementation may be an attractive therapeutic strategy in patients with early-stage myeloid malignancies and precursor conditions.”