Vitamin D insufficiency and clinical outcomes with chimeric antigen receptor T-cell therapy in large B-cell lymphoma Journal Article
| Authors: | Nath, K.; Tomas, A. A.; Flynn, J.; Fein, J. A.; Alperovich, A.; Anagnostou, T.; Batlevi, C. L.; Dahi, P. B.; Fingrut, W. B.; Giralt, S. A.; Lin, R. J.; Palomba, M. L.; Peled, J. U.; Salles, G.; Sauter, C. S.; Scordo, M.; Fraint, E.; Feuer, E.; Shah, N.; Slingerland, J. B.; Devlin, S.; Shah, G. L.; Gupta, G.; Perales, M. A.; Shouval, R. |
| Article Title: | Vitamin D insufficiency and clinical outcomes with chimeric antigen receptor T-cell therapy in large B-cell lymphoma |
| 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. © 2022 The American Society for Transplantation and Cellular Therapy |
| Keywords: | adult; cancer survival; controlled study; aged; survival rate; major clinical study; overall survival; histopathology; cancer recurrence; neurotoxicity; outcome assessment; follow up; cell viability; progression free survival; relapse; practice guideline; in vitro study; histology; central nervous system; germinal center; karnofsky performance status; gamma interferon; vitamin d; remission; vitamin d deficiency; virus infection; hematopoietic stem cell; large cell lymphoma; lymphoma, large b-cell, diffuse; biological therapy; observational study; prognostic biomarker; cd19 antigen; vitamin blood level; vitamin; cumulative incidence; leukapheresis; clinical outcome; overall response rate; vitamins; 25 hydroxyvitamin d; diffuse large b cell lymphoma; large b-cell lymphoma; humans; human; male; female; article; cell- and tissue-based therapy; car-t; chemiluminescence immunoassay; tisagenlecleucel t; chimeric antigen receptor t-cell immunotherapy; axicabtagene ciloleucel; lisocabtagene maraleucel; receptors, chimeric antigen |
| Journal Title: | Transplantation and Cellular Therapy |
| Volume: | 28 |
| Issue: | 11 |
| ISSN: | 2666-6375 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2022-11-01 |
| Start Page: | 751.e1 |
| End Page: | 751.e7 |
| Language: | English |
| DOI: | 10.1016/j.jtct.2022.08.001 |
| PUBMED: | 35944603 |
| PROVIDER: | scopus |
| PMCID: | PMC9637764 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 December 2022 -- Source: Scopus |
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