P-039: Vitamin D Deficiency and Clinical Outcomes with Chimeric Antigen Receptor T-Cell Therapy in Relapsed/Refractory Multiple Myeloma

Introduction: Vitamin D (VitD) deficiency is a potentially modifiable risk factor for poor outcomes in relapsed/refractory multiple myeloma (RRMM). Recent studies demonstrated that VitD deficiency may be associated with inferior survival in recipients of autologous stem-cell transplant (ASCT) (Eicher, Hem Onc, 2020). Additionally, we previously demonstrated that VitD insufficiency is associated with inferior clinical outcomes in patients with B-cell lymphoma treated with CD19-directed chimeric antigen receptor T-cell therapy (CAR-T) (Nath, TCT, 2022). The role of circulating vitamin D in patients with RRMM treated with CAR-T is currently unknown. Here, we evaluated the impact of vitamin D status on clinical outcomes in this patient population.

Methods: We performed a single-center, retrospective analysis of adult patients with RRMM who received commercial or investigational CAR-T between 04/2017–09/2022 and had a serum vitamin D (25[OH]D) measured pre-CAR-infusion. Vitamin D deficiency was defined as < 20ng/mL as per the Endocrine Society guidelines. Cox proportional hazards models were used to assess the impact of pre-CAR-T vitamin D status on progression-free survival (PFS) and overall survival (OS).

Results: Of the 102 patients with RRMM who received CAR-T, 61 patients had a pre-CAR infusion vitamin D level available. The median age of the 61 patients was 62 years (range, 38-79), with 57% males. Patients were heavily pretreated with a median 6 prior lines of therapy (range, 2 – 14), and 97% had a prior ASCT. Triple-class refractoriness (TCR), extramedullary disease (EMD), and high-risk cytogenetics (HRC) were observed in 80%, 52%, and 70% of patients, respectively. Baseline characteristics were overall comparable between vitamin D deficient ( < 20ng/mL; n= 11) and vitamin D replete (≥20ng/mL; n=50) patients. On univariate analysis, vitamin D deficient compared to replete patients had a significantly inferior PFS (median PFS, 3.5 months vs. 6.5months, HR of 2.24, 95% Confidence Interval [CI] 1.09-4.59, p=0.041). These differences-maintained significance in a multivariate analysis adjusting for baseline characteristics (age, gender, ECOG performance status, HRC, EMD, penta-refractory status) (HR of 2.53, 95%CI 1.14–5.66, p=0.032). There was no significant difference in OS based on vitamin D status in both the univariate and multivariate analysis. Only EMD and decreased performance status (ECOG 1 or 2) was an independently significant poor prognostic factor for OS.

Conclusions: In this modest cohort of patients with RRMM, VitD deficiency ( < 20ng/mL) prior to CAR-T cell therapy was potentially associated with inferior PFS. However, the small sample size and the possibility of residual confounding precludes concrete conclusions. Future studies with larger cohorts of patients will be needed to confirm these findings.