New research suggests that supplementation with vitamins C and D appears beneficial for patients with acute myeloid leukemia (AML) who are undergoing intensive chemotherapy. Supplementation during chemotherapy was associated with a lower rate of grade 3-4 adverse events (AEs), and, in the case of patients with an NPM1 mutation, a better overall survival (OS) compared to patients with the mutation who did not receive supplementation. The findings were published in Blood Advances.
In their retrospective monocentric study of 431 patients (262 receiving no supplementation and 169 receiving supplementation), the investigators administered vitamin C (1 g x 2/day, three times a week; intravenous) and vitamin D3 (cholecalciferol: 100,000 IU/week; orally). The researchers noted that the weekly doses of vitamin D were at levels in the higher range of vitamin D repletion practices for allogeneic hematopoietic cell transplantation. When they performed regular monitoring of blood calcium levels, however, they found no evidence of hypercalcemia.
Patients in the supplementation group had reduced AEs during induction chemotherapy as compared with those who did not receive supplementation, respectively:
- bacterial infections: 27.2% vs. 35.1%; p=0.086
- fungal infections: 10.1% vs. 18.3%; p=0.019
- hemorrhage: 1.8% vs. 5.7%; p=0.045
- macrophage activation syndrome: 1.8% vs. 8.8%; p=0.002
The investigators saw no difference, however, in response rate, relapse rate, relapse incidence, and OS between the two groups. They also noted that although two drugs (midostaurin and CPX-351) were introduced during the most recent study period, they did not see any significant effect of these drugs on survival.
Certain recurrent gene mutations are known to transform hematopoietic progenitors into AML cells. When the investigators tested interactions between these mutations and control versus the vitamin C/D group, the multivariate analysis revealed a significant interaction between vitamin C/D and NPM1 mutation, such that vitamin C/D supplementation was significantly and independently associated with better OS in patients with NPM1 mutations (hazard ratio = 0.52; 95% CI 0.30-0.90; p=0.019) as compared to those without the mutation.
Corresponding author Christian Recher, MD, of Université Toulouse III Paul Sebatier in France, said the study was not powered to analyze the subgroup of patients with specific TET2 mutations, a situation he found unfortunate given that vitamin C is a cofactor of TET2.
While research has demonstrated the role of vitamin C in normal hematopoiesis and leukemogenesis and vitamin D in inducing myeloid progenitor differentiation in monocytes, very few studies have assessed vitamin C and D levels upon diagnosis of AML. Even fewer studies have assessed the effect of these vitamins on AML outcomes.
“We found a schema to restore normal vitamin D levels before transplantation, which may be important since patients with vitamin D insufficiency have been shown to relapse more frequently after transplantation,” Dr. Recher said, adding that he and his colleagues continue to use vitamin therapy for their patients.
He also noted that he was surprised by the significant interaction between NPM1 mutations and vitamin C/D therapy and called the finding “very intriguing.” While he and his colleagues suspect that vitamin D may induce differentiation in AML cells with the NPM1 mutation, the team does not yet have strong data to support the hypothesis.
“Vitamins C and D have long been tested in other cancers without clear breakthrough,” Dr. Recher said. In the case of AML, however, he said there is a specific reason to think that supplementing these vitamins may benefit the patient.
Although the study demonstrated a benefit from vitamin supplementation, the authors note that the concomitant use of both vitamins makes it difficult to determine whether the value is associated with one or the other vitamin or the combination of the two. Dr. Recher thus calls for an AML clinical trial to further investigate the benefits of vitamins C and D supplementation in the patient population.
Any conflicts of interest declared by the authors can be found in the original article.
Reference
Mouchel PL, Bérard E, Tavitian S, et al. Vitamin C and D supplementation in acute myeloid leukemia [published online ahead of print, 2023 Sept 6]. Blood Adv. doi: 10.1182/bloodadvances.2023010559.
