Abstract
Vitamin D deficiency has been reported to be a negative prognostic factor in elderly patients with aggressive B‐cell lymphomas. In vitro data suggest that vitamin D supplementation may enhance rituximab‐mediated cytotoxicity. We prospectively assessed 25‐hydroxyvitamin D [25(OH)D] levels at diagnosis in a cohort of 155 patients with aggressive B‐cell lymphomas of whom 128 had diffuse large B‐cell lymphoma (DLBCL) not otherwise specified. 25(OH)D levels were deficient (<20 ng/mL) in 105 (67%), insufficient (20–29 ng/mL) in 32 (21%), and normal (≥30 ng/mL) in 18 (12%) patients with a seasonal variation. Patient characteristics associated with lower 25(OH)D levels were poor performance status, overweight, B‐symptoms, elevated LDH, lower albumin and hemoglobin levels. As a result of a change in practice pattern, 116 patients received vitamin D3 (cholecalciferol) supplementation that included a loading phase with daily replacement and subsequent maintenance phase with a weekly dose of 25,000 IU until end of treatment. This resulted in a significant increase in 25(OH)D levels, with normalization in 56% of patients. We analyzed the impact of 25(OH)D levels on event‐free survival in patients treated with Rituximab‐CHOP. 25(OH)D levels below 20 ng/mL at diagnosis and IPI were independently associated with inferior EFS. Moreover, patients with normalized 25(OH)D levels following supplementation showed better EFS than patients with persistently deficient/insufficient 25(OH)D levels. Our study provides the first evidence that achievement of normal 25(OH)D levels after vitamin D3 supplementation is associated with improved outcome in patients with DLBCL and deficient/insufficient 25(OH)D levels when receiving rituximab‐based treatment.
Highlights
Treatment results of diffuse large B-cell lymphoma (DLBCL) have significantly improved after the introduction of immunotherapy with the monoclonal CD20 antibody rituximab, added to traditional chemotherapy regimens [1, 2]
We considered whether oral supplementation with vitamin D3 would rapidly restore 25(OH) D levels to normal range, and changed our practice pattern to supplement vitamin D3
We designed a supplementation regimen that started with a loading phase consisting of a 1-w eek course of daily vitamin D supplementation, that we extended to 2 weeks in patients with severely deficient levels (
Summary
Treatment results of diffuse large B-cell lymphoma (DLBCL) have significantly improved after the introduction of immunotherapy with the monoclonal CD20 antibody rituximab, added to traditional chemotherapy regimens [1, 2]. An association between levels of vitamin D and lymphoma mortality has been reported for patients with DLBCL [3]. Data from the German RICOVER-60 study indicated that vitamin D deficiency is a negative prognostic factor for elderly patients with DLBCL, treated with rituximab-containing chemotherapy (R-CHOP) [4]. Low serum vitamin D levels were identified as negative prognostic factor for survival in a retrospective analysis of cohorts of patients with follicular lymphoma (FL) [5]. The main blood circulation form of vitamin D is 25-hydroxyvitamin D3 [25(OH)D], and its level is a good indicator of vitamin D status. Vitamin D deficiency, defined as a serum 25(OH)D level below 10 ng/mL, is very
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