Vitamin D Deficiency Linked to Poorer Outcomes in Diffuse Large B-Cell Lymphoma

New Orleans, LA — Researchers at ASH presented data that showed patients with diffuse large B-cell lymphoma (DLBCL) who had deficient vitamin D levels—defined as serum 25-hydroxyvitamin (25-OH-VitD) <25 ng/mL&mdash;had poorer outcomes than patients with normal vitamin D levels. Vitamin D deficiency was independently associated with a 1.5-fold greater risk of disease progression and twice the risk of death. “These are some of the strongest findings yet between vitamin D and cancer outcome,” said lead investigator Matthew Drake, MD, PhD, an endocrinologist at the Mayo Clinic in Rochester, Minnesota.

Vitamin D deficiency is a common problem in the United States, even in states with more annual sunshine. “If you look at the entire united states population, anywhere between 30% and 50% of people have vitamin D levels which we would consider to be below the optimal range,” Dr Drake said. He added that there were many reasons but lifestyle was probably the most significant, with people spending a majority of their time indoors. There is no clear consensus on the threshold for vitamin D deficiency, but the researchers selected 25 ng/mL because at that level, the body begins leaching calcium from the bone.

The study looked at 2 cohorts of patients. Cohort 1 included 374 patients (median age, 62 years) enrolled in the University of Iowa/Mayo Clinic Lymphoma SPORE Molecule Epidemiology Resource observational study who received a DLBCL diagnosis between September 2002—February 2008; treatment was not part of the study protocol, but 83% of patients underwent immunochemotherapy. Cohort 2 consisted of 62 patients (median age, 61 years) whose DLBCL was diagnosed between February 2006—August 2007; these patients were enrolled in the NCCTG clinical trial N0489, a single-arm study investigating the safety and efficacy of epratuzumab plus rituximab (Rituxan) plus CHOP21. Patients were followed similarly in both groups, for event-free survival (EFS), with events defined as progression, retreatment, or death due to any cause; and overall survival (OS).

Vitamin D levels were measured prior to treatment in 59% of the SPORE patients and in all the N0489 patients. Half the SPORE patients had vitamin D deficiency and 24% of the N0489 patients, consistent across all patient demographics. After a median follow-up of 3 years, Cohort 1 experienced 95 deaths and 131 events. Median follow-up for N0489 was 2 years, which reported 13 deaths and 18 events.

Investigators concluded that there was a significant association between vitamin D deficiency and inferior OS (hazard ratio [HR], 2.33; 95% confidence interval [CI], 1.53-3.57; logrank P = .00001) and EFS (HR, 1.71; 95% CI, 1.20-2.44; logrank P = .003) in the SPORE cohort. They saw similar results regarding EFS in the N0489 cohort, but the small sample size was too small to attribute significance to the data.

Co-author David E. Witzig, MD, also of the Mayo Clinic in Rochester, described the results as intriguing. “Vitamin D is an important vitamin; it’s important to our immune system, and it’s affecting, perhaps, the way these patients are able to fight their tumor,” he stated in a press release.

Other studies have linked vitamin D deficiency to outcomes in cancer;

. This is the first study to look at a connection between vitamin D deficiency and outcomes in lymphoma. According to Dr Drake, vitamin D has been identified as critical to gene regulation, cell growth, and apoptosis. “Whether or not vitamin D deficiency plays a role in lymphoma, we really can’t say at this point,” he said.

we reported on a study from the Breast Cancer Symposium in October that found an association between breast cancer and low levels of vitamin D

This does not mean hematologic oncologists should not rush to start their patients with DLBCL on vitamin D supplementation, according to the authors. “While these findings are very provocative, they are preliminary and need to be validated in other studies,” Dr Drake said.

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ASH Abstract 1952