PMID- 35944603 OWN - NLM STAT- MEDLINE DCOM- 20221107 LR - 20231102 IS - 2666-6367 (Electronic) IS - 2666-6375 (Print) IS - 2666-6367 (Linking) VI - 28 IP - 11 DP - 2022 Nov TI - Vitamin D Insufficiency and Clinical Outcomes with Chimeric Antigen Receptor T-Cell Therapy in Large B-cell Lymphoma. PG - 751.e1-751.e7 LID - S2666-6367(22)01517-2 [pii] LID - 10.1016/j.jtct.2022.08.001 [doi] AB - 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; 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. CI - Copyright (c) 2022 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved. FAU - Nath, Karthik AU - Nath K AD - Department of Medicine, Adult Bone Marrow Transplantation Service, Memorial Sloan Kettering Cancer Center, New York, New York. FAU - Tomas, Ana Alarcon AU - Tomas AA AD - Department of Medicine, Adult Bone Marrow Transplantation Service, Memorial Sloan Kettering Cancer Center, New York, New York; PhD Program in Signals Integration and Modulation in Biomedicine, Cell therapy and Translational Medicine, University of Murcia, Murcia, Spain. FAU - Flynn, Jessica AU - Flynn J AD - Department of Biostatistics and Epidemiology, Memorial Sloan Kettering Cancer Center, New York, New York. FAU - Fein, Joshua A AU - Fein JA AD - University of Connecticut Medical Center, Farmington, Connecticut. FAU - Alperovich, Anna AU - Alperovich A AD - Department of Medicine, Adult Bone Marrow Transplantation Service, Memorial Sloan Kettering Cancer Center, New York, New York. FAU - Anagnostou, Theodora AU - Anagnostou T AD - Department of Medicine, Adult Bone Marrow Transplantation Service, Memorial Sloan Kettering Cancer Center, New York, New York. FAU - Batlevi, Connie Lee AU - Batlevi CL AD - Department of Medicine, Lymphoma Service, Memorial Sloan Kettering Cancer Center, New York, New York; Weill Cornell Medical College, New York, New York. FAU - Dahi, Parastoo B AU - Dahi PB AD - Department of Medicine, Adult Bone Marrow Transplantation Service, Memorial Sloan Kettering Cancer Center, New York, New York; Weill Cornell Medical College, New York, New York. FAU - Fingrut, Warren B AU - Fingrut WB AD - Department of Medicine, Adult Bone Marrow Transplantation Service, Memorial Sloan Kettering Cancer Center, New York, New York. FAU - Giralt, Sergio A AU - Giralt SA AD - Department of Medicine, Adult Bone Marrow Transplantation Service, Memorial Sloan Kettering Cancer Center, New York, New York; Weill Cornell Medical College, New York, New York. FAU - Lin, Richard J AU - Lin RJ AD - Department of Medicine, Adult Bone Marrow Transplantation Service, Memorial Sloan Kettering Cancer Center, New York, New York; Weill Cornell Medical College, New York, New York. FAU - Palomba, M Lia AU - Palomba ML AD - Department of Medicine, Lymphoma Service, Memorial Sloan Kettering Cancer Center, New York, New York; Weill Cornell Medical College, New York, New York. FAU - Peled, Jonathan U AU - Peled JU AD - Department of Medicine, Adult Bone Marrow Transplantation Service, Memorial Sloan Kettering Cancer Center, New York, New York; Weill Cornell Medical College, New York, New York. FAU - Salles, Gilles AU - Salles G AD - Department of Medicine, Lymphoma Service, Memorial Sloan Kettering Cancer Center, New York, New York; Weill Cornell Medical College, New York, New York. FAU - Sauter, Craig S AU - Sauter CS AD - Department of Medicine, Adult Bone Marrow Transplantation Service, Memorial Sloan Kettering Cancer Center, New York, New York; Weill Cornell Medical College, New York, New York. FAU - Scordo, Michael AU - Scordo M AD - Department of Medicine, Adult Bone Marrow Transplantation Service, Memorial Sloan Kettering Cancer Center, New York, New York; Weill Cornell Medical College, New York, New York. FAU - Fraint, Ellen AU - Fraint E AD - Department of Pediatrics, Stem Cell Transplantation and Cellular Therapies Program, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Pediatric Hematology, Oncology and Cellular Therapy, Children's Hospital at Montefiore, Bronx, New York. FAU - Feuer, Elise AU - Feuer E AD - Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York. FAU - Shah, Nishi AU - Shah N AD - Department of Medicine, Adult Bone Marrow Transplantation Service, Memorial Sloan Kettering Cancer Center, New York, New York. FAU - Slingerland, John B AU - Slingerland JB AD - Department of Medicine, Adult Bone Marrow Transplantation Service, Memorial Sloan Kettering Cancer Center, New York, New York. FAU - Devlin, Sean AU - Devlin S AD - Department of Biostatistics and Epidemiology, Memorial Sloan Kettering Cancer Center, New York, New York. FAU - Shah, Gunjan L AU - Shah GL AD - Department of Medicine, Adult Bone Marrow Transplantation Service, Memorial Sloan Kettering Cancer Center, New York, New York; Weill Cornell Medical College, New York, New York. FAU - Gupta, Gaurav AU - Gupta G AD - Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York. FAU - Perales, Miguel-Angel AU - Perales MA AD - Department of Medicine, Adult Bone Marrow Transplantation Service, Memorial Sloan Kettering Cancer Center, New York, New York; Weill Cornell Medical College, New York, New York. FAU - Shouval, Roni AU - Shouval R AD - Department of Medicine, Adult Bone Marrow Transplantation Service, Memorial Sloan Kettering Cancer Center, New York, New York; Weill Cornell Medical College, New York, New York. Electronic address: shouvalr@mskcc.org. LA - eng GR - K08 HL143189/HL/NHLBI NIH HHS/United States GR - P30 CA008748/CA/NCI NIH HHS/United States PT - Journal Article PT - Observational Study PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20220806 PL - United States TA - Transplant Cell Ther JT - Transplantation and cellular therapy JID - 101774629 RN - 0 (Receptors, Chimeric Antigen) RN - 0 (Vitamins) RN - 1406-16-2 (Vitamin D) SB - IM MH - Adult MH - Humans MH - *Receptors, Chimeric Antigen/therapeutic use MH - *Lymphoma, Large B-Cell, Diffuse MH - Vitamins/therapeutic use MH - Vitamin D/therapeutic use MH - *Vitamin D Deficiency/drug therapy MH - Cell- and Tissue-Based Therapy PMC - PMC9637764 MID - NIHMS1839919 OTO - NOTNLM OT - CAR-T OT - Large B-cell lymphoma OT - Prognostic biomarker OT - Vitamin D COIS- Disclosure of Conflicts of Interest Roni Shouval. Consulting or Advisory Role: Medexus, MyBiotics; Connie Lee Batlevi Stock and Other Ownership Interests: Moderna Therapeutics, Novavax, Pfizer, Bristol Myers Squibb, Regeneron, Viatris. Honoraria: DAVA Oncology. Consulting or Advisory Role: LifeSci Capital, GLG, Juno Therapeutics, Celgene, Seattle Genetics, Kite, a Gilead company, TG Therapeutics, Karyopharm Therapeutics. Research Funding: Janssen Biotech (Inst), Novartis (Inst), Epizyme (Inst), Xynomic Pharma (Inst), Bayer (Inst), Roche (Inst), Autolus (Inst). Open Payments Link: https://openpaymentsdata.cms.gov/physician/2778694; Parastoo B. Dahi. Consulting or Advisory Role: Kite, a Gilead company; Sergio A. Giralt. Honoraria: Celgene, Takeda, Amgen, Jazz Pharmaceuticals, Sanofi. Consulting or Advisory Role: Celgene, Takeda, Sanofi, Jazz Pharmaceuticals, Amgen, Janssen, Actinuum, Bristol Myers Squibb, Johnson & Johnson, Pfizer. Research Funding: Celgene (Inst), Miltenyi Biotec, Johnson & Johnson, Amgen, Actinuum, Sanofi. Travel, Accommodations, Expenses: Celgene, Sanofi, Amgen, Jazz Pharmaceuticals; Gilles Salles. Honoraria: Roche/Genentech, Janssen, Celgene, Gilead Sciences, Novartis, AbbVie, MorphoSys. Consulting or Advisory Role: Roche/Genentech, Gilead Sciences, Janssen, Celgene, Novartis, MorphoSys, Epizyme, Alimera Sciences, Genmab, Debiopharm Group, Velosbio, BMS, BeiGene, Incyte, Miltenyi Biotec, Ipsen; Craig S. Sauter. Consulting or Advisory Role: Spectrum Pharmaceuticals, Juno Therapeutics, Sanofi, Gilead Sciences, Novartis Precision BioSciences, Gamida Cell, Karyopharm Therapeutics, GlaxoSmithKline, Genmab. Research Funding: Juno Therapeutics (Inst), Sanofi (Inst), Precision BioSciences (Inst), BMS (Inst), Actinium Pharmaceuticals (Inst). Travel, Accommodations, Expenses: Juno Therapeutics, Sanofi, Gilead Sciences, Novartis; Michael Scordo. Honoraria: i3 CME. Consulting or Advisory Role: McKinsey & Company, Angiocrine Bioscience, Omeros. Research Funding: Angiocrine Bioscience, Omeros (Inst). Travel, Accommodations, Expenses: Kite/Gilead; Gunjan L. Shah. Research Funding: Amgen (Inst), Janssen (Inst); Miguel-Angel Perales. Stock and Other Ownership Interests: NexImmune and Omeros. Honoraria: MorphoSys. Consulting or Advisory Role: Incyte, Merck, Servier/Pfizer, NexImmune, Novartis, MolMed, Medigene, Takeda, Nektar, AbbVie, Cidara Therapeutics, Celgene, Kite/Gilead, Bristol Myers Squibb, Omeros, Vor Biopharma. Research Funding: Incyte (Inst), Miltenyi Biotec (Inst), Novartis (Inst), Kite, a Gilead company (Inst), Nektar (Inst); Maria Lia Palomba. Stock and Other Ownership Interests: Seres Therapeutics (I). Honoraria: Flagship Biosciences (I), Evelo Therapeutics (I), Jazz Pharmaceuticals (I), Therakos (I), Amgen (I), Merck (I), Seres Therapeutics (I). Consulting or Advisory Role: Flagship Biosciences (I), Novartis (I), Evelo Therapeutics (I), Jazz Pharmaceuticals (I), Therakos (I), Amgen (I), Merck (I), Seres Therapeutics (I), Kite, a Gilead company, Novartis, BeiGene, Synthekine. Research Funding: Seres Therapeutics (I) Patents, Royalties, Other Intellectual Property: Intellectual Property Rights (I), Juno intellectual property rights (Inst); Jonathan U. Peled. Research funding, intellectual property fees, and travel reimbursement: Seres Therapeutics. Consulting fees: DaVolterra, CSL Behring, and from MaaT Pharma. Advisory board and holds equity in Postbiotics Plus Research; No other potential conflicts of interest were reported by the other co-authors. EDAT- 2022/08/10 06:00 MHDA- 2022/11/08 06:00 PMCR- 2023/11/01 CRDT- 2022/08/09 19:23 PHST- 2022/03/28 00:00 [received] PHST- 2022/07/16 00:00 [revised] PHST- 2022/08/01 00:00 [accepted] PHST- 2022/08/10 06:00 [pubmed] PHST- 2022/11/08 06:00 [medline] PHST- 2022/08/09 19:23 [entrez] PHST- 2023/11/01 00:00 [pmc-release] AID - S2666-6367(22)01517-2 [pii] AID - 10.1016/j.jtct.2022.08.001 [doi] PST - ppublish SO - Transplant Cell Ther. 2022 Nov;28(11):751.e1-751.e7. doi: 10.1016/j.jtct.2022.08.001. Epub 2022 Aug 6.