Maintenance Vitamin D Supplementation in Combination with Lenalidomide Maintenance Following Autologous Stem Cell Transplantation in Newly Diagnosed Multiple Myeloma

Vitamin D deficiency is common among patients with multiple myeloma and may adversely affect immune function, bone health, and recovery following autologous stem cell transplantation (ASCT). Vitamin D plays an important role in immune regulation and may influence the reconstitution of innate and adaptive immunity after transplantation. However, the clinical impact of maintaining adequate vitamin D levels during post-transplant recovery remains unclear. This prospective randomized clinical trial evaluates whether vitamin D supplementation following ASCT improves immune reconstitution and clinical outcomes, including infection rates, treatment tolerability, and disease control. Furthermore, the promising antimyeloma activity and favorable toxicity profile of vitamin D in combination with lenalidomide provide a strong rationale for evaluating this combination as maintenance therapy after ASCT. Given the low cost, accessibility, and favorable safety profile of vitamin D, this strategy could represent a practical adjunct to standard lenalidomide maintenance while potentially enhancing immune recovery and improving long-term outcomes in patients with multiple myeloma.

This IRB-approved, randomized, parallel-assignment interventional trial is being conducted at the Georgia Cancer Center. Patients undergoing ASCT are randomized to maintenance vitamin D supplementation or no maintenance vitamin D. In both groups, vitamin D deficiency is initially corrected with weekly cholecalciferol 50,000 IU until serum vitamin D levels exceed 30 ng/mL. This study is designed to have stratified randomization by race (AA vs Non-AA) and baseline vitamin D level. Patients randomized to the maintenance arm will subsequently receive monthly cholecalciferol 50,000 IU, whereas supplementation is discontinued in the comparator arm with continued monitoring of vitamin D levels. Following ASCT, both groups receive standard lenalidomide maintenance, administered at 10 mg daily during the first three 28-day cycles and 15 mg daily beginning with cycle 4.

The primary endpoint is lymphocyte subset reconstitution at 120 days following ASCT, including absolute CD3, CD4, CD8, and NK cell counts. Secondary endpoints include progression-free survival and overall survival at 3 years; overall response rates and measurable residual disease (MRD) status at 120 days and 2 years post-ASCT. Vitamin D levels before ASCT, at 120 days, and its correlation with neutrophils/platelet engraftment; and transfusion independence with other transplant-related morbidity and mortality. This trial is ongoing, and no clinical trial results are currently available for presentation.

This trial-in-progress study will evaluate the potential role of vitamin D maintenance as a supportive intervention following ASCT and may provide insight into the relationship between vitamin D status, immune reconstitution, and clinical outcomes in multiple myeloma.