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Multicenter Study
. 2023 Sep 12;7(17):4765-4772.
doi: 10.1182/bloodadvances.2022008937.

Chimeric antigen receptor T-cell therapy yields similar outcomes in patients with and without cytokine release syndrome

Shakthi T Bhaskar  1 , Vivek G Patel  1 , David L Porter  2 , Stephen J Schuster  2 , Loretta J Nastoupil  3 , Miguel-Angel Perales  4   5 , Ana Alarcon Tomas  4   6 , Michael R Bishop  7 , Joseph P McGuirk  8 , Richard T Maziarz  9 , Andy I Chen  9 , Veronika Bachanova  10 , Joseph E Maakaron  10 , Peter A Riedell  7 , Olalekan O Oluwole  1
Affiliations
Multicenter Study

Chimeric antigen receptor T-cell therapy yields similar outcomes in patients with and without cytokine release syndrome

Shakthi T Bhaskar et al. Blood Adv. .

Abstract

Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment of many patients with aggressive relapsed or refractory large B-cell lymphoma (LBCL). Treatment can be complicated by clinically evident cytokine release syndrome (CRS), which is characterized by the development of fever, hypoxia, and hypotension, and can be life-threatening. Most patients treated with CAR-T cells develop CRS, which is thought to represent an immune phenomenon. It was previously unknown whether patients who did not develop CRS had reduced CAR-T cell activity and were therefore likely to have worse outcomes. We conducted a multicenter retrospective analysis of 352 adult patients treated at 8 academic medical centers in the United States who received axicabtagene ciloleucel or tisagenlecleucel for the treatment of LBCL. The outcomes of interest included progression-free survival, overall survival, complete response rate, and overall response rate. Of the included patients, 262 (74.4%) developed CRS. There was no significant difference in progression-free survival (P = .99) or overall survival (P = .16) between patients who developed CRS and those who did not develop CRS. Peak ferritin levels >5000 ng/mL during treatment and lactate dehydrogenase levels greater than the institutional upper limit of normal before lymphodepleting chemotherapy were associated with significantly worse progression-free and overall survival in the multivariate analysis. There was no significant difference in the complete response or overall response rates between patients who did and did not develop CRS. In this retrospective analysis, we report that patients who develop CRS have clinical outcomes similar to those of patients without CRS treated with commercial anti-CD19 CAR-T cells.

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Conflict of interest statement

Conflict-of-interest disclosure: D.L.P. reports honorarium for consulting or advisory board participation from Novartis, Kite/Gilead, Incyte, Gerson Lehrman Group, Janssen (Johnson & Johnson), Jazz, Adepcet Bio, DeCART, Bristol Myers Squibb (BMS), bluebird bio, Kadmon, Angiocrine, and Mirror Biologics; research support from Novartis; patents and royalties related to CAR T-cell therapy for malignancies licensed to Novartis and Tmunity; and stock/equity in Genentech/Roche (spouse former employment). S.J.S. reports membership on the advisory board for BeiGene, Celgene/BMS/Juno, Genentech, Roche, Genmab, Incyte, Janssen, MorphoSys, Mustang Biotech, and Novartis; research grants from Genentech/Roche, Merck, and Novartis; is a member on the steering committee for Fate Therapeutics, Legend Biotech, and Nordic Nanovector; received honoraria from Incyte and Novartis; consults for Novartis; and reports a patent on “combination therapies of CAR and PD-1 inhibitors” with royalties paid to Novartis. L.J.N. reports honoraria from ADC Therapeutics, BMS, Caribou Biosciences, Epizyme, Genentech, Gilead/Kite, Janssen, MorphoSys, Novartis, and Takeda, and research support from BMS, Caribou Biosciences, Epizyme, Genentech, Genmab, Gilead/Kite, Janssen, IGM Biosciences, Novartis, and Takeda. M.-A.P. reports honoraria from AbbVie, AlloVir, Astellas, BMS, Celgene, Equilium, Exevir, Incyte, Karyopharm, Kite/Gilead, Merck, Miltenyi Biotec, MorphoSys, Novartis, Nektar Therapeutics, Omeros, OrcaBio, Takeda, VectivBio AG, and Vor Biopharma; serves on data and safety monitoring boards (DSMBs) for Cidara Therapeutics, Medigene, Sellas Life Sciences, and Servier, serves on the scientific advisory board of NexImmune; has ownership interests in NexImmune and Omeros; and received institutional research support for clinical trials from Incyte, Kite/Gilead, Miltenyi Biotec, Nektar Therapeutics, and Novartis. M.R.B. reports membership on an advisory board or consultancy for Kite/Gilead, Novartis, CRISPR Therapeutics, Autolus Therapeutics, BMS, Incyte, Sana Biotechnology, Iovance Biotherapeutics, and served on a speakers bureau for BMS, Sanofi, Agios, and Incyte. J.P.M. reports honoraria for consulting or advisory board participation for Kite, BMS, Novartis, Caribou, AlloVir, NEKTAR, Janssen. R.T.M. is an advisor or consultant for AlloVir, CRISPR Therapeutics, Incyte, and Novartis; reports honoraria from Incyte; research support from AlloVir, and Novartis; participation in a data and safety monitoring board for Athersys, Vor Pharma, and Novartis; a patent with Athersys, Inc; and serves on the scientific advisory board of Artiva and Lyrik Therapeutics. A.I.C. reports institutional research funding from Novartis and Fate Therapeutics and is an advisor for Kite. V.B. reports research funding from Incyte, BMS, Gamide Cell, Incyte, Citius Pharmaceuticals, Fate Therapeutics; consultancy with Incyte, Karyopharma, ADC, BMS, Gamida Cell, Fate Therapeutics and DSMB; and membership at Miltenyi Biotec. J.E.M. receives institutional research funding from Gilead, CRISPR, Precision BioSciences, Scripps, Fate Therapeutics, ADC. P.A.R. reports research support/funding from BMS, Kite Pharma, Inc/Gilead, MorphoSys, Calibr, Tessa Therapeutics, Fate Therapeutics, Xencor, and Novartis Pharmaceuticals Corporation; speaker’s bureau from Kite Pharma, Inc/Gilead; consultancy on advisory boards of AbbVie, Novartis Pharmaceuticals Corporation, BMS, Janssen, BeiGene, Karyopharm Therapeutics Inc, Takeda Pharmaceutical Company, Kite Pharma, Inc/Gilead, Sana Biotechnology, Nektar Therapeutics, Intellia Therapeutics, and Bayer; and received honoraria from Novartis Pharmaceuticals Corporation. O.O.O. reports consultancy with and serves on the advisory boards for Pfizer, Kite, Gilead, AbbVie, Janssen, TGR Therapeutics, ADC, Novartis, Curio Science, Nektar; receives institution funding from Kite, Pfizer, Daichi Sankyo, Allogene; and receives honoraria from Pfizer and Gilead. The remaining authors declare no competing financial interests.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Progression-free survival. Kaplan-Meier curve showing progression-free survival in patients treated with CD19-directed CAR-T cells showing similar curves for those who did and did not develop cytokine release syndrome.
Figure 2.
Figure 2.
Overall survival. Kaplan-Meier curve showing overall survival in patients treated with CD19-directed CAR-T cells showing similar curves for patients who did and did not develop cytokine release syndrome.
Figure 3.
Figure 3.
Overall survival stratified by CRS grade. Kaplan-Meier curve showing overall survival for patients who received axicabtagene ciloleucel, showing no significant difference in survival when stratified by CRS grade.
See this image and copyright information in PMC

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