Vitamin D Deficient Follicular Lymphoma Patients Experience Higher Relapse Risk

Jonathan W. Friedberg, MD

Low vitamin D levels prior to treatment may be linked to risk of relapse or death for patients with follicular lymphoma (FL), according to a new study published online in the Journal of Clinical Oncology.

“Our data, replicated internationally, support other published observations linking vitamin D deficiency with inferior cancer outcomes,” said Jonathan W. Friedberg, MD, co-leader of the study, in a statement. Friedberg is director of the Wilmot Cancer Institute at the University of Rochester Medical Center.

For the study, researchers observed a total of 423 patients with FL in two independent cohorts: SWOG, part of the NCI’s National Clinical Trials Network, and the Lymphoma Study Association (LYSA) based in France. Researchers measured the patients’ baseline vitamin D blood levels before cancer treatment began and then tracked and analyzed cancer survival data for each group over a minimum median follow-up of 5.5 years.

The researchers found that the adjusted progression-free survival (PFS) hazard ratio [HR] for the 15% of patients in the SWOG cohort who were vitamin D deficient, defined as <20 ng/mL, was 1.97 (95% CI, 1.10-3.53). The overall survival (OS) HR for the vitamin D—deficient patients in the SWOG cohort was 4.16 (95% CI, 1.66-10.44).

For patients in the LYSA cohort who were vitamin D deficient (<10 ng/mL; 25% of cohort), the adjusted HR for PFS was 1.50 (85% CI, 0.93-2.42); the adjusted HR for OS among these patients was 1.92 (95% CI, 0.72-5.13).

“Although statistical significance was not reached in the LYSA cohort, the consistent estimates of association between low vitamin D levels and follicular lymphoma outcomes in two independent cohorts suggest the serum vitamin D might be the first potentially modifiable factor to be associated with follicular lymphoma survival,” the authors wrote.

Large differences in vitamin D levels among the patients in the two cohorts prevented scientists from being able to recommend an optimal level of vitamin D for patients with FL, but future research might support prescribing vitamin D supplements for patients at the earliest point of FL treatment, when patients are typically monitored closely but have not begun active therapy. It has also been theorized that vitamin D may represent a proxy or biomarker for better health going into cancer treatment.

“However, the mechanisms of this link are likely complex and require further study,” Friedberg said.

Prior studies have shown a survival benefit among patients with higher vitamin D levels for diffuse large B-cell lymphoma and chronic lymphocytic leukemia. It has also been found that low levels of vitamin D among women with breast cancer correlated with more aggressive tumors and poorer prognosis, and that a vitamin D deficiency among African Americans may help to explain higher death rates from colorectal cancer.

FL is generally incurable, although it is slow-growing, and many people live for years with the disease. While treatments have improved, a subset of patients can have an aggressive form of the disease for which therapy is not as effective.

Better ways to predict the course of the disease are needed, and this is where vitamin D levels might provide a previously unidentified but modifiable factor associated with prognosis, Friedberg said.

Kelly JL, Salles G, Goldman B, et al. Low serum vitamin D levels are associated with inferior survival in follicular lymphoma: a prospective evaluation in SWOG and LYSA studies [published online March 30, 2015]. J Clin Oncol.