In a study reported in the Journal of Clinical Oncology, Borchmann et al found that pretreatment vitamin D deficiency was associated with poorer progression-free and overall survival rates in patients receiving first-line treatment for Hodgkin lymphoma.

“On the basis of our clinical and preclinical findings, we encourage that vitamin D screening and replacement be incorporated into future randomized clinical trials to properly clarify the role of vitamin D replacement therapy in [Hodgkin lymphoma].”

— Borchmann et al

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Study Details

The analysis involved 351 patients receiving first-line treatment in three German Hodgkin Study Group trials (HD7, HD8, and HD9). Serum vitamin D levels were categorized as sufficient (≥ 50 nmol/L), insufficient (≥ 30 and < 50 nmol/L), and deficient (< 30 nmol/L). Median follow-up was 13 years.

Baseline Vitamin D and Outcomes

Overall, 50% of patients had vitamin D deficiency, 24% had vitamin D insufficiency, and 26% had vitamin D sufficiency prior to treatment. Vitamin D deficiency was more common in patients with relapsed or refractory disease vs matched relapse-free controls (68% vs 41%, P < .001; median baseline levels = 21.4 nmol/L vs 35.5 nmol/L). 

Progression-free and overall survival were similar among patients with sufficient vs insufficient vitamin D levels. For vitamin D deficient vs insufficient/sufficient patients, progression-free survival was 74.4% vs 84.6% at 5 years and 64.2% vs 81.8% at 10 years (10-year difference = 17.6%, hazard ratio [HR] = 2.13, P <.001). Overall survival was 87.4% vs 89.4% at 5 years and 76.1% vs 87.2% at 10 years (10-year difference = 11.1%, HR = 1.82, P < .001). Findings were consistent across trials and treatment groups. The investigators noted that the difference in overall survival primarily reflected a higher proportion of Hodgkin lymphoma-related deaths in patients with vitamin D deficiency.

Preclinical Findings

In preclinical studies to assess whether vitamin D might play a role in chemosensitivity in Hodgkin lymphoma, the investigators found that treatment of cultured Hodgkin lymphoma cell lines with physiologic doses of vitamin D (calcitriol) in combination with chemotherapy resulted in increased antiproliferative effects. In a Hodgkin lymphoma xenograft model, treatment with vitamin D (dietary supplement, cholecalciferol) plus chemotherapy reduced tumor growth rate compared with either alone.

The investigators concluded, “On the basis of our clinical and preclinical findings, we encourage that vitamin D screening and replacement be incorporated into future randomized clinical trials to properly clarify the role of vitamin D replacement therapy in [Hodgkin lymphoma].”

Sven Borchmann, MD, of German Hodgkin Study Group, University Hospital of Cologne, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: For full disclosures of the study authors, visit jco.ascopubs.org.