Abstract
Introduction. Vitamin D deficiency has been linked to reduced survival in cancer patients, though evidence is still inconclusive. In lymphomas, it shows potential as a predictive and prognostic biomarker, with studies suggesting an association between low vitamin D levels and poorer outcomes, including reduced response to first-line chemotherapy in Western and Asian regions. Currently, no standardized tools exist to predict early treatment response or guide therapy adjustments. Validating vitamin D in Latin American patients could have important public health benefits, such as supporting supplementation to improve outcomes. Given its ease of use, vitamin D assessment could be readily adopted in clinical practice across Latin America. Therefore, this study aimed to evaluate whether vitamin D levels at diagnosis are associated with objective response rate (ORR) and overall survival (OS) in aggressive lymphoma patients. Methods. We conducted a prospective, multicenter cohort study involving adults (≥18 years) diagnosed with aggressive lymphomas between 2021 and 2022 at three academic cancer centers in Peru. Vitamin D levels were measured at diagnosis. Cutoff values for vitamin D dichotomization were obtained using the maximally selected rank statistic for survival data. ORR was assessed in the mid and at the end of the tratment and was defined as the proportion of patients achieving a complete or partial response. OS was defined as the time from diagnosis to death from any cause. Statistical analyses included Kaplan-Meier survival curves, and Cox proportional hazards models. Results A total of 125 patients were enrolled, including 110 with B-cell lymphomas: 60 cases of diffuse large B-cell lymphoma (53%), 15 of follicular lymphoma (12%), and 29 of other B-cell subtypes (23%). Additionally, there were 8 patients with Hodgkin lymphoma and 7 with aggressive T-cell lymphomas, comprising 3 cases of adult T-cell leukemia/lymphoma, 1 peripheral T-cell lymphoma, not otherwise specified, and 1 subcutaneous panniculitis-like T-cell lymphoma.Overall, the median age was 63 years (range: 26–90), 56% were male, 54% were over 60 years old, and 63.8% presented with stage III–IV disease. In our population, a vitamin D cutoff of 9.5 ng/mL was identified, with 9% (n=11) classified as vitamin D deficient (≤9.5 ng/mL) and 91% (n=113) with sufficient Vitamin D levels (>9.5 ng/mL). Vitamin D deficiency was associated with higher ECOG (≥2, p=0.002), elevated LDH (p=0.03), low serum albumin (<3.5 g/dL, p=0.003), and higher red cell distribution width (>14%, p=0.016) at diagnosis. Patients with Vitamin D deficiency showed significantly lower ORR at mid-treatment (55% vs. 91%, p < 0.001). However, when analyzing Vitamin D as a continuous variable, no significant difference in ORR was found at the end of treatment (66% vs. 84%, p = 0.122). With a median follow-up of 21 months, patients with Vitamin D ≤9.5 ng/mL had significantly lower 2-year OS in univariabe analysis (55% vs. 77%; Hazard ratio [HR]: 3.4, 95% confidence interval [CI]: 1.29–9.18, p=0.014). This association, however, lost statistical significance in multivariable analysis (adjusted HR: 1.34, 95% CI: 0.47–3.83, p=0.591). Conclusion. Vitamin D levels at diagnosis may reflect a more aggressive disease phenotype and could serve as a useful biomarker for identifying high-risk patients. Although vitamin D deficiency does not appear to significantly influence treatment response (ORR) or OS in patients with aggressive lymphomas, monitoring vitamin D status may assist clinicians in risk stratification and optimizing supportive care. However, further follow-up and validation in larger, multicenter cohorts across Latin America are essential, as most existing evidence comes from studies conducted in other regions.
