Vitamin D status appeared to be an independent predictor of clinical outcomes and may affect chemosensitivity among patients with Hodgkin lymphoma, according to results of a prospective case-control study published in Journal of Clinical Oncology.
Based on the results, vitamin D screening and replacement should be incorporated into future randomized trials involving patients with Hodgkin lymphoma, researchers wrote.
“We found increased [Hodgkin lymphoma] mortality and incidence in winter months at higher latitudes,” Sven Borchmann, MD, of the German Hodgkin Study Group and department of internal medicine at University of Cologne in Germany, told HemOnc Today. “Despite a recognized seasonal pattern of incidence and mortality in Hodgkin lymphoma, vitamin D deficiency has not been thoroughly evaluated in Hodgkin lymphoma.”
Borchmann and colleagues evaluated pretreatment vitamin D levels and clinical outcomes of 351 patients with various stages of Hodgkin lymphoma in three German Hodgkin Study Group trials who had been randomly assigned to receive first-line chemotherapy with or without radiotherapy. Researchers matched each case with documented relapse or progressive disease with two nonrelapsed controls.
Describing pretreatment vitamin D status among patients across all stages of disease, comparing baseline vitamin D status between cases and controls, and reporting how baseline vitamin D status impacted PFS and OS served as the study’s primary objectives.
Researchers used 25-hydroxyvitamin D as a marker of vitamin D status.
Half of the patients (n = 175; median age, 32 years; 58% male) exhibited vitamin D deficiency (< 30 nmol/L) before planned chemotherapy, whereas 83 patients (median age, 33 years; 67% male) were vitamin D insufficient ( 30 nmol/L to < 50 nmol/L) and 93 patients (median age, 31 years; 56% male) were vitamin D sufficient ( 50 nmol/L).
Results showed a greater proportion of patients with relapsed or refractory Hodgkin lymphoma had pretreatment vitamin D deficiency than matched relapse-free controls (68% vs. 41%; P < .001; median baseline vitamin D, 21.4 nmol/L vs. 35.5 nmol/L).
Patients with vitamin D deficiency had inferior PFS (10-year difference, 17.6%; HR = 2.13; 95% CI, 1.84-2.48) and OS (10-year difference, 11.1%; HR = 1.82; 95% CI, 1.53 to 2.15) than patients who were not vitamin D deficient. These results remained consistent across trial groups.
In subsequent experiments with cultured Hodgkin lymphoma cell lines, researchers found supplementing physiologic doses of vitamin D (calcitriol) increased antiproliferative effects in combination with chemotherapy. In a Hodgkin lymphoma xenograft mouse model, supplemental vitamin D (cholecalciferol) improved tumor chemosensitivity by reducing the rate of tumor growth compared with vitamin D or chemotherapy alone.
“This is likely not [limited to] Hodgkin lymphoma,” Borchmann said. “There is plenty of evidence for such a link in solid tumors or other hematological malignancies. However, the magnitude of the effect we observed in our study is quite strong and surprised us compared with other studies in other malignancies.” – by John DeRosier
For more information:
Sven Borchmann, MD, can be reached at firstname.lastname@example.org.
Disclosures: Borchmann reports honoraria, institutional research funding or travel expenses from Bristol-Myers Squibb and Takeda. Please see the study for all other authors’ relevant financial disclosures.