Vitamin D Insufficiency and Clinical Outcomes with Chimeric Antigen Receptor T-Cell Therapy in Large B-cell Lymphoma

Karthik Nath, Ana Alarcon Tomas, Jessica Flynn, Joshua A. Fein, Anna Alperovich, Theodora Anagnostou, Connie Lee Batlevi, Parastoo B. Dahi, Warren B. Fingrut, Sergio A. Giralt, Richard J. Lin, M. Lia Palomba, Jonathan U. Peled, Gilles Salles, Craig S. Sauter, Michael Scordo, Ellen Fraint, Elise Feuer, Nishi Shah, John B. SlingerlandSean Devlin, Gunjan L. Shah, Gaurav Gupta, Miguel Angel Perales, Roni Shouval

Research output: Contribution to journalArticlepeer-review

Abstract

Vitamin D insufficiency is a potentially modifiable risk factor for poor outcomes in newly diagnosed large B-cell lymphoma (LBCL). However, the role of circulating vitamin D concentrations in relapsed/refractory LBCL treated with CD19-directed chimeric antigen receptor T-cell therapy (CAR-T) is currently unknown. This was a single-center, observational study that evaluated the association of pre-CAR-T 25-hydroxyvitamin D (25-OHD) status with 100-day complete response, progression-free survival, overall survival, and CAR-T–related toxicity in 111 adult relapsed/refractory LBCL patients. Vitamin D insufficiency was defined as ≤30 ng/mL in accordance with the Endocrine Society guidelines. The median pre-CAR-T 25-hydroxyvitamin D concentration was 24 ng/mL (interquarile range = 18-34). Vitamin D–insufficient patients (≤30 ng/mL; n = 73 [66%]) were significantly younger than their vitamin D–replete (>30 ng/mL; n = 38 [34%]) counterparts (P= .039). The vitamin D–insufficient cohort was enriched for de novo LBCL as the histological subtype (P= .026) and had a higher proportion of tisagenlecleucel as the CAR-T product (P= .049). There were no other significant differences in the baseline characteristics between the two groups. In vitamin D–insufficient compared to –replete patients, 100-day complete response was 55% versus 76% (P= .029), and 2-year overall survival was 41% versus 71% (P= .061), respectively. In multivariate analysis, vitamin D insufficiency remained significantly associated with 100-day complete response (odds ratio 2.58 [1.05-6.83]; P= .045) and overall survival (hazard ratio 2.24 [1.08-4.66], P= .030). In recipients of tisagenlecleucel, vitamin D insufficiency was associated with significantly lower cell viability of the infused CAR-T product (P= .015). Finally, pretreatment vitamin D insufficiency did not predict for subsequent CAR-T–related toxicity. This is the first report to demonstrate that vitamin D insufficiency is associated with inferior clinical outcomes in CAR-T recipients. Further study into the mechanistic insights of this finding, and the potential role of vitamin D supplementation to optimize CAR-T are warranted.

Original languageEnglish (US)
Pages (from-to)751.e1-751.e7
JournalTransplantation and Cellular Therapy
Volume28
Issue number11
DOIs
StatePublished - Nov 2022
Externally publishedYes

Keywords

  • CAR-T
  • Large B-cell lymphoma
  • Prognostic biomarker
  • Vitamin D

ASJC Scopus subject areas

  • Immunology and Allergy
  • Molecular Medicine
  • Hematology
  • Cell Biology
  • Transplantation

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