From the Journals

Vitamin D deficiency appears to worsen survival in Hodgkin lymphoma



Vitamin D deficiency is associated with worse progression-free and overall survival among patients with Hodgkin lymphoma, according to new study findings.

Sven Borchmann, MD, of the University of Cologne (Germany) and German Hodgkin Study Group and coauthors conducted a case-control study of 351 patients enrolled in the German Hodgkin Study Group trials who had available baseline serum samples. Pretreatment vitamin D levels were assessed and categorized as deficient (less than 30 nmol/L), insufficient (30-49 nmol/L), or sufficient (50 nmol/L or greater). The findings were published in the Journal of Clinical Oncology.

The researchers found that before starting treatment, 50% of patients were vitamin D deficient.

Patients with baseline vitamin D deficiency had significantly lower progression-free survival – 10.2% lower at 5 years and 17.6% lower at 10 years – compared with patients with either sufficient or insufficient vitamin D levels (P less than .001). They also had 2% lower overall survival at 5 years and 11.1% lower overall survival at 10 years (P less than .001).

The researchers also conducted preclinical studies in effort to understand the effect of vitamin D on Hodgkin lymphoma cells and in Hodgkin lymphoma tumor models.

They explored the effect of vitamin D on cultured Hodgkin lymphoma cell lines and saw a dose-response effect of calcitriol in reducing cell proliferation rates. They then looked at the effect of calcitriol on cell lines that were also exposed to doxorubicin or etoposide, and found calcitriol improved the cytotoxicity of these chemotherapy agents, especially at lower doses.

Finally, they conducted an in-vivo mouse study using Hodgkin lymphoma xenografts, and looked at whether vitamin D supplementation increased the effect of doxorubicin or etoposide. This revealed that chemotherapy and vitamin D supplementation together were significantly better at controlling tumor growth, compared with monotherapy with either vitamin D or doxorubicin and compared with placebo.

“On the basis of our study results and the limited toxicity of vitamin D replacement therapy, we would advocate for vitamin D deficiency screening and replacement to be incorporated into future randomized clinical trials to properly clarify the role of vitamin D replacement in HL [Hodgkin lymphoma],” the researchers wrote. “The goal of these trials should be to determine whether vitamin D replacement in HL improves outcome.”

No study funding information was reported. Dr. Borchmann reported honoraria and research funding from Takeda. Other authors reported financial disclosures related to Takeda, Roche, Bristol-Myers Squibb, and other companies.

SOURCE: Borchmann S et al. J Clin Oncol. 2019 Oct 17. doi:10.1200/JCO.19.00985.

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