Patterns of Use, Outcomes, and Resource Utilization among Recipients of Commercial Axicabtagene Ciloleucel and Tisagenlecleucel for Relapsed/Refractory Aggressive B Cell Lymphomas

Peter A. Riedell; Wei Ting Hwang; Loretta J. Nastoupil; Martina Pennisi; Joseph P. McGuirk; Richard T. Maziarz; Veronika Bachanova; Olalekan O. Oluwole; Jamie Brower; Oscar A. Flores; Nausheen Ahmed; Levanto Schachter; Kharmen Bharucha; Bhagirathbhai R. Dholaria; Stephen J. Schuster; Miguel Angel Perales; Michael R. Bishop; David L. Porter

doi:10.1016/j.jtct.2022.07.011

Patterns of Use, Outcomes, and Resource Utilization among Recipients of Commercial Axicabtagene Ciloleucel and Tisagenlecleucel for Relapsed/Refractory Aggressive B Cell Lymphomas

Peter A. Riedell, Wei Ting Hwang, Loretta J. Nastoupil, Martina Pennisi, Joseph P. McGuirk, Richard T. Maziarz, Veronika Bachanova, Olalekan O. Oluwole, Jamie Brower, Oscar A. Flores, Nausheen Ahmed, Levanto Schachter, Kharmen Bharucha, Bhagirathbhai R. Dholaria, Stephen J. Schuster, Miguel Angel Perales, Michael R. Bishop, David L. Porter

Research output: Contribution to journal › Article › peer-review

43 Scopus citations

Abstract

Axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) are CD19-directed chimeric antigen receptor (CAR) T cell therapies approved for the treatment of relapsed/refractory aggressive B cell lymphomas. We present a multicenter retrospective study among centers that prescribe either commercial product to evaluate usage patterns, safety and efficacy outcomes, and resource utilization. Data collection included all patients from 8 US centers who underwent apheresis between May 1, 2018, and July 31, 2019. Patient selection, toxicity management, and disease assessment followed institutional practices. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were graded according to American Society for Transplantation and Cellular Therapy consensus criteria, and tumor responses were assessed according to the Lugano 2014 classification scheme. A total of 260 patients underwent apheresis, including 168 (65%) for axi-cel and 92 (35%) for tisa-cel. Among the infused patients, the median age was 59 years for axi-cel recipients and 67 years for tisa-cel recipients (P < .001). The median time from apheresis to infusion was 28 days for axi-cel recipients and 45 days for tisa-cel recipients (P < .001). Sixty-one percent of the axi-cel recipients and 43% of the tisa-cel recipients would have been ineligible for the ZUMA-1 and JULIET trials, respectively. Grade ≥3 CRS occurred in 9% of axi-cel recipients and in 1% of tisa-cel recipients (P = .017), and grade ≥3 ICANS was seen in 38% of axi-cel recipients and 1% of tisa-cel recipients (P < .001). Inpatient cell therapy infusion was common (92% in axi-cel recipients, 37% in tisa-cel recipients). The day 90 overall response rate was 52% in the axi-cel group and 41% in the tisa-cel group (P =. 113), with complete response in 44% and 35%, respectively (P =. 319). Twelve-month progression-free survival (42% versus 32%; P =. 206) and overall survival (62% versus 59%; P =. 909) rates were comparable in the axi-cel and tisa-cel groups. Baseline characteristics differed between the 2 groups, although response rates and survival outcomes were comparable, albeit lower than those in the pivotal trials. Safety and resource utilization appear to be key differentiators between axi-cel and tisa-cel.

Original language	English (US)
Pages (from-to)	669-676
Number of pages	8
Journal	Transplantation and Cellular Therapy
Volume	28
Issue number	10
DOIs	https://doi.org/10.1016/j.jtct.2022.07.011
State	Published - Oct 2022

Bibliographical note

Funding Information:
The authors thank the data managers at each Cell Therapy Consortium member institution who collected patient data and maintained the database. Financial disclosure: This research was supported in part by a grant from Novartis Pharmaceuticals (to D.L.P.), National Cancer Institute Grant P30 CA008748 (to M.A.P.), and National Center for Advancing Translational Sciences Award UL1-TR002494 (to V.B.). M.P. was supported by an American-Italian Cancer Foundation Postdoctoral Research Fellowship and by the Associazione italiana contro le leucemie-linfomi e mieloma Milano e Provincia ONLUS. Conflict of interest statement: P.A.R. reports research support/funding from BMS, Kite Pharma/Gilead, MorphoSys, Calibr, Tessa Therapeutics, Fate Therapeutics, Xencor, and Novartis Pharmaceuticals; serving on speakers bureaus for Kite Pharma/Gilead; consultancy on advisory boards for AbbVie, Novartis Pharmaceuticals, BMS, Janssen, BeiGene, Karyopharm Therapeutics, Takeda Pharmaceutical, Kite Pharma/Gilead, Sana Biotechnology, Nektar Therapeutics, Intellia Therapeutics, and Bayer; and honoraria from Novartis Pharmaceuticals. W-T.H. reports research support/funding from Novartis. L.J.N. reports research support/funding from BMS/Celgene, Caribou Biosciences, Epizyme, Genentech, Kite Pharma/Gilead, IGM Biosciences, Janssen, Novartis, Takeda, and TG Therapeutics; honoraria from ADC Therapeutics, Bayer, BMS/Celgene, Epizyme, Genentech, Kite Pharma/Gilead, Janssen, Morphosys, Novartis, Takeda, and TG Therapeutics. J.P.M. reports honoraria from Kite Pharma/Gilead, Juno Therapeutics, Allovir, Magenta Therapeutics, EcoR1 Capital, Janssen, and BMS/Celgene and research funding from Astellas Pharma, Bellicum Pharmaceuticals, Gamida Cell, Pluristem Therapeutics, Kite Pharma/Gilead, and Allovir. R.T.M. reports serving as advisor or consultant for Allovir, Artiva, CRISPR Therapeutics, Incyte, and Novartis; honoraria from Bristol-Myers Squibb, Incyte, Intellia, and Kite Pharma/Gilead; research support from BMS, Allovir, and Novartis; participation on a data and safety monitoring board for Athersys, Vor Pharma, and Novartis; and a patent with Athersys. V.B. reports research support from Incyte, Gamida Cell, and BMS; scientific advisory board membership for Gamida Cell, and Karyopharm; and participation on a data and safety monitoring board for Miltenyi Biotec. O.O.O. reports consultancy from Pfizer, Kite Pharma/Gilead, AbbVie, Janssen, TGR Therapeutics, Novartis, and Curio Science and institutional research funding from Kite Pharma/Gilead, Pfizer, and Daiichi Sankyo. B.R.D. reports institutional research funding from Takeda, Janssen, Angiocrine, Pfizer, Poseida, MEI, and Orcabio; consultancy/advisory board membership for Jazz, Gamida Cell, MJH BioScience, and Arivan Research. S.J.S. reports research funding from AbbVie, Adaptive Biotechnologies, Celgene, DTRM, Genentech, Roche, Juno Therapeutics, Merck, Novartis, Incyte, Pharmacyclics and TG Therapeutics; honoraria from Celgene and Novartis; consultancy for AstraZeneca, BeiGene, Celgene, Genentech, Genmab, Fate Therapeutics, Roche, Incyte, Juno Therapeutics, Legend Biotech, Loxo Oncology, Morphosys, Mustang Biotech, Nordic Nanovector, Novartis, and Regeneron; and patents related to CD19 CAR T cells and autologous costimulated T cells. M-A.P. reports honoraria from AbbVie, Astellas, Bristol-Myers Squibb, Celgene, Equilium, Incyte, Karyopharm, Kite Pharma/Gilead, Merck, Miltenyi Biotec, MorphoSys, Novartis, Nektar Therapeutics, Omeros, OrcaBio, Takeda, VectivBio AG, and Vor Biopharma; participation on a data and safety monitoring board for Cidara Therapeutics, Medigene, Sellas Life Sciences, and Servier and the scientific advisory board of NexImmune; ownership interests in NexImmune and Omeros; and research support for clinical trials from Incyte, Kite Pharma/Gilead, Miltenyi Biotec, and Novartis. M.R.B. reports membership on an advisory board or consultancy for Kite Pharma/Gilead, Novartis, CRISPR Therapeutics, Autolus Therapeutics, BMS, Incyte, Sana Biotechnology, and Iovance Biotherapeutics; serving on a speakers bureau for BMS, Kite/Gilead, Agios, and Incyte. D.L.P. reports honoraria for consulting or advisory board participation from Novartis, Kite Pharma/Gilead, Incyte, Gerson Lehrman Group, Janssen (Johnson & Johnson), Jazz, Adepcet Bio, DeCART, BMS, Bluebird Bio, and Kadmon; 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's former employer). The other authors report no conflicts of interest. Authorship statement: Conception and design: P.A.R. D.L.P. Collection and assembly of data: W-TH, JB, PAR Data analysis and interpretation: All authors. Manuscript writing: first draft, P.A.R. and D.L.P; revisions, all authors; final approval of manuscript, all authors. Financial disclosure: See Acknowledgments on page 675.

Funding Information:
Financial disclosure: This research was supported in part by a grant from Novartis Pharmaceuticals (to D.L.P.), National Cancer Institute Grant P30 CA008748 (to M.A.P.), and National Center for Advancing Translational Sciences Award UL1-TR002494 (to V.B.). M.P. was supported by an American-Italian Cancer Foundation Postdoctoral Research Fellowship and by the Associazione italiana contro le leucemie-linfomi e mieloma Milano e Provincia ONLUS.

Publisher Copyright:
© 2022 The American Society for Transplantation and Cellular Therapy

Keywords

Aggressive large B cell lymphoma
CAR T cell therapy outcomes
CAR T cell toxicity
Chimeric antigen receptor T cell therapy
Resource utilization

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.jtct.2022.07.011

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Riedell, P. A., Hwang, W. T., Nastoupil, L. J., Pennisi, M., McGuirk, J. P., Maziarz, R. T., Bachanova, V., Oluwole, O. O., Brower, J., Flores, O. A., Ahmed, N., Schachter, L., Bharucha, K., Dholaria, B. R., Schuster, S. J., Perales, M. A., Bishop, M. R., & Porter, D. L. (2022). Patterns of Use, Outcomes, and Resource Utilization among Recipients of Commercial Axicabtagene Ciloleucel and Tisagenlecleucel for Relapsed/Refractory Aggressive B Cell Lymphomas. Transplantation and Cellular Therapy, 28(10), 669-676. https://doi.org/10.1016/j.jtct.2022.07.011

Patterns of Use, Outcomes, and Resource Utilization among Recipients of Commercial Axicabtagene Ciloleucel and Tisagenlecleucel for Relapsed/Refractory Aggressive B Cell Lymphomas. / Riedell, Peter A.; Hwang, Wei Ting; Nastoupil, Loretta J. et al.
In: Transplantation and Cellular Therapy, Vol. 28, No. 10, 10.2022, p. 669-676.

Research output: Contribution to journal › Article › peer-review

Riedell, PA, Hwang, WT, Nastoupil, LJ, Pennisi, M, McGuirk, JP, Maziarz, RT, Bachanova, V, Oluwole, OO, Brower, J, Flores, OA, Ahmed, N, Schachter, L, Bharucha, K, Dholaria, BR, Schuster, SJ, Perales, MA, Bishop, MR & Porter, DL 2022, 'Patterns of Use, Outcomes, and Resource Utilization among Recipients of Commercial Axicabtagene Ciloleucel and Tisagenlecleucel for Relapsed/Refractory Aggressive B Cell Lymphomas', Transplantation and Cellular Therapy, vol. 28, no. 10, pp. 669-676. https://doi.org/10.1016/j.jtct.2022.07.011

@article{02ac18497819426f96bd77846fac7e4a,

title = "Patterns of Use, Outcomes, and Resource Utilization among Recipients of Commercial Axicabtagene Ciloleucel and Tisagenlecleucel for Relapsed/Refractory Aggressive B Cell Lymphomas",

abstract = "Axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) are CD19-directed chimeric antigen receptor (CAR) T cell therapies approved for the treatment of relapsed/refractory aggressive B cell lymphomas. We present a multicenter retrospective study among centers that prescribe either commercial product to evaluate usage patterns, safety and efficacy outcomes, and resource utilization. Data collection included all patients from 8 US centers who underwent apheresis between May 1, 2018, and July 31, 2019. Patient selection, toxicity management, and disease assessment followed institutional practices. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were graded according to American Society for Transplantation and Cellular Therapy consensus criteria, and tumor responses were assessed according to the Lugano 2014 classification scheme. A total of 260 patients underwent apheresis, including 168 (65%) for axi-cel and 92 (35%) for tisa-cel. Among the infused patients, the median age was 59 years for axi-cel recipients and 67 years for tisa-cel recipients (P < .001). The median time from apheresis to infusion was 28 days for axi-cel recipients and 45 days for tisa-cel recipients (P < .001). Sixty-one percent of the axi-cel recipients and 43% of the tisa-cel recipients would have been ineligible for the ZUMA-1 and JULIET trials, respectively. Grade ≥3 CRS occurred in 9% of axi-cel recipients and in 1% of tisa-cel recipients (P = .017), and grade ≥3 ICANS was seen in 38% of axi-cel recipients and 1% of tisa-cel recipients (P < .001). Inpatient cell therapy infusion was common (92% in axi-cel recipients, 37% in tisa-cel recipients). The day 90 overall response rate was 52% in the axi-cel group and 41% in the tisa-cel group (P =. 113), with complete response in 44% and 35%, respectively (P =. 319). Twelve-month progression-free survival (42% versus 32%; P =. 206) and overall survival (62% versus 59%; P =. 909) rates were comparable in the axi-cel and tisa-cel groups. Baseline characteristics differed between the 2 groups, although response rates and survival outcomes were comparable, albeit lower than those in the pivotal trials. Safety and resource utilization appear to be key differentiators between axi-cel and tisa-cel.",

keywords = "Aggressive large B cell lymphoma, CAR T cell therapy outcomes, CAR T cell toxicity, Chimeric antigen receptor T cell therapy, Resource utilization",

author = "Riedell, {Peter A.} and Hwang, {Wei Ting} and Nastoupil, {Loretta J.} and Martina Pennisi and McGuirk, {Joseph P.} and Maziarz, {Richard T.} and Veronika Bachanova and Oluwole, {Olalekan O.} and Jamie Brower and Flores, {Oscar A.} and Nausheen Ahmed and Levanto Schachter and Kharmen Bharucha and Dholaria, {Bhagirathbhai R.} and Schuster, {Stephen J.} and Perales, {Miguel Angel} and Bishop, {Michael R.} and Porter, {David L.}",

note = "Funding Information: The authors thank the data managers at each Cell Therapy Consortium member institution who collected patient data and maintained the database. Financial disclosure: This research was supported in part by a grant from Novartis Pharmaceuticals (to D.L.P.), National Cancer Institute Grant P30 CA008748 (to M.A.P.), and National Center for Advancing Translational Sciences Award UL1-TR002494 (to V.B.). M.P. was supported by an American-Italian Cancer Foundation Postdoctoral Research Fellowship and by the Associazione italiana contro le leucemie-linfomi e mieloma Milano e Provincia ONLUS. Conflict of interest statement: P.A.R. reports research support/funding from BMS, Kite Pharma/Gilead, MorphoSys, Calibr, Tessa Therapeutics, Fate Therapeutics, Xencor, and Novartis Pharmaceuticals; serving on speakers bureaus for Kite Pharma/Gilead; consultancy on advisory boards for AbbVie, Novartis Pharmaceuticals, BMS, Janssen, BeiGene, Karyopharm Therapeutics, Takeda Pharmaceutical, Kite Pharma/Gilead, Sana Biotechnology, Nektar Therapeutics, Intellia Therapeutics, and Bayer; and honoraria from Novartis Pharmaceuticals. W-T.H. reports research support/funding from Novartis. L.J.N. reports research support/funding from BMS/Celgene, Caribou Biosciences, Epizyme, Genentech, Kite Pharma/Gilead, IGM Biosciences, Janssen, Novartis, Takeda, and TG Therapeutics; honoraria from ADC Therapeutics, Bayer, BMS/Celgene, Epizyme, Genentech, Kite Pharma/Gilead, Janssen, Morphosys, Novartis, Takeda, and TG Therapeutics. J.P.M. reports honoraria from Kite Pharma/Gilead, Juno Therapeutics, Allovir, Magenta Therapeutics, EcoR1 Capital, Janssen, and BMS/Celgene and research funding from Astellas Pharma, Bellicum Pharmaceuticals, Gamida Cell, Pluristem Therapeutics, Kite Pharma/Gilead, and Allovir. R.T.M. reports serving as advisor or consultant for Allovir, Artiva, CRISPR Therapeutics, Incyte, and Novartis; honoraria from Bristol-Myers Squibb, Incyte, Intellia, and Kite Pharma/Gilead; research support from BMS, Allovir, and Novartis; participation on a data and safety monitoring board for Athersys, Vor Pharma, and Novartis; and a patent with Athersys. V.B. reports research support from Incyte, Gamida Cell, and BMS; scientific advisory board membership for Gamida Cell, and Karyopharm; and participation on a data and safety monitoring board for Miltenyi Biotec. O.O.O. reports consultancy from Pfizer, Kite Pharma/Gilead, AbbVie, Janssen, TGR Therapeutics, Novartis, and Curio Science and institutional research funding from Kite Pharma/Gilead, Pfizer, and Daiichi Sankyo. B.R.D. reports institutional research funding from Takeda, Janssen, Angiocrine, Pfizer, Poseida, MEI, and Orcabio; consultancy/advisory board membership for Jazz, Gamida Cell, MJH BioScience, and Arivan Research. S.J.S. reports research funding from AbbVie, Adaptive Biotechnologies, Celgene, DTRM, Genentech, Roche, Juno Therapeutics, Merck, Novartis, Incyte, Pharmacyclics and TG Therapeutics; honoraria from Celgene and Novartis; consultancy for AstraZeneca, BeiGene, Celgene, Genentech, Genmab, Fate Therapeutics, Roche, Incyte, Juno Therapeutics, Legend Biotech, Loxo Oncology, Morphosys, Mustang Biotech, Nordic Nanovector, Novartis, and Regeneron; and patents related to CD19 CAR T cells and autologous costimulated T cells. M-A.P. reports honoraria from AbbVie, Astellas, Bristol-Myers Squibb, Celgene, Equilium, Incyte, Karyopharm, Kite Pharma/Gilead, Merck, Miltenyi Biotec, MorphoSys, Novartis, Nektar Therapeutics, Omeros, OrcaBio, Takeda, VectivBio AG, and Vor Biopharma; participation on a data and safety monitoring board for Cidara Therapeutics, Medigene, Sellas Life Sciences, and Servier and the scientific advisory board of NexImmune; ownership interests in NexImmune and Omeros; and research support for clinical trials from Incyte, Kite Pharma/Gilead, Miltenyi Biotec, and Novartis. M.R.B. reports membership on an advisory board or consultancy for Kite Pharma/Gilead, Novartis, CRISPR Therapeutics, Autolus Therapeutics, BMS, Incyte, Sana Biotechnology, and Iovance Biotherapeutics; serving on a speakers bureau for BMS, Kite/Gilead, Agios, and Incyte. D.L.P. reports honoraria for consulting or advisory board participation from Novartis, Kite Pharma/Gilead, Incyte, Gerson Lehrman Group, Janssen (Johnson & Johnson), Jazz, Adepcet Bio, DeCART, BMS, Bluebird Bio, and Kadmon; 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's former employer). The other authors report no conflicts of interest. Authorship statement: Conception and design: P.A.R. D.L.P. Collection and assembly of data: W-TH, JB, PAR Data analysis and interpretation: All authors. Manuscript writing: first draft, P.A.R. and D.L.P; revisions, all authors; final approval of manuscript, all authors. Financial disclosure: See Acknowledgments on page 675. Funding Information: Financial disclosure: This research was supported in part by a grant from Novartis Pharmaceuticals (to D.L.P.), National Cancer Institute Grant P30 CA008748 (to M.A.P.), and National Center for Advancing Translational Sciences Award UL1-TR002494 (to V.B.). M.P. was supported by an American-Italian Cancer Foundation Postdoctoral Research Fellowship and by the Associazione italiana contro le leucemie-linfomi e mieloma Milano e Provincia ONLUS. Publisher Copyright: {\textcopyright} 2022 The American Society for Transplantation and Cellular Therapy",

year = "2022",

month = oct,

doi = "10.1016/j.jtct.2022.07.011",

language = "English (US)",

volume = "28",

pages = "669--676",

journal = "Transplantation and Cellular Therapy",

issn = "2666-6367",

publisher = "Elsevier BV",

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}

TY - JOUR

T1 - Patterns of Use, Outcomes, and Resource Utilization among Recipients of Commercial Axicabtagene Ciloleucel and Tisagenlecleucel for Relapsed/Refractory Aggressive B Cell Lymphomas

AU - Riedell, Peter A.

AU - Hwang, Wei Ting

AU - Nastoupil, Loretta J.

AU - Pennisi, Martina

AU - McGuirk, Joseph P.

AU - Maziarz, Richard T.

AU - Bachanova, Veronika

AU - Oluwole, Olalekan O.

AU - Brower, Jamie

AU - Flores, Oscar A.

AU - Ahmed, Nausheen

AU - Schachter, Levanto

AU - Bharucha, Kharmen

AU - Dholaria, Bhagirathbhai R.

AU - Schuster, Stephen J.

AU - Perales, Miguel Angel

AU - Bishop, Michael R.

AU - Porter, David L.

N1 - Funding Information: The authors thank the data managers at each Cell Therapy Consortium member institution who collected patient data and maintained the database. Financial disclosure: This research was supported in part by a grant from Novartis Pharmaceuticals (to D.L.P.), National Cancer Institute Grant P30 CA008748 (to M.A.P.), and National Center for Advancing Translational Sciences Award UL1-TR002494 (to V.B.). M.P. was supported by an American-Italian Cancer Foundation Postdoctoral Research Fellowship and by the Associazione italiana contro le leucemie-linfomi e mieloma Milano e Provincia ONLUS. Conflict of interest statement: P.A.R. reports research support/funding from BMS, Kite Pharma/Gilead, MorphoSys, Calibr, Tessa Therapeutics, Fate Therapeutics, Xencor, and Novartis Pharmaceuticals; serving on speakers bureaus for Kite Pharma/Gilead; consultancy on advisory boards for AbbVie, Novartis Pharmaceuticals, BMS, Janssen, BeiGene, Karyopharm Therapeutics, Takeda Pharmaceutical, Kite Pharma/Gilead, Sana Biotechnology, Nektar Therapeutics, Intellia Therapeutics, and Bayer; and honoraria from Novartis Pharmaceuticals. W-T.H. reports research support/funding from Novartis. L.J.N. reports research support/funding from BMS/Celgene, Caribou Biosciences, Epizyme, Genentech, Kite Pharma/Gilead, IGM Biosciences, Janssen, Novartis, Takeda, and TG Therapeutics; honoraria from ADC Therapeutics, Bayer, BMS/Celgene, Epizyme, Genentech, Kite Pharma/Gilead, Janssen, Morphosys, Novartis, Takeda, and TG Therapeutics. J.P.M. reports honoraria from Kite Pharma/Gilead, Juno Therapeutics, Allovir, Magenta Therapeutics, EcoR1 Capital, Janssen, and BMS/Celgene and research funding from Astellas Pharma, Bellicum Pharmaceuticals, Gamida Cell, Pluristem Therapeutics, Kite Pharma/Gilead, and Allovir. R.T.M. reports serving as advisor or consultant for Allovir, Artiva, CRISPR Therapeutics, Incyte, and Novartis; honoraria from Bristol-Myers Squibb, Incyte, Intellia, and Kite Pharma/Gilead; research support from BMS, Allovir, and Novartis; participation on a data and safety monitoring board for Athersys, Vor Pharma, and Novartis; and a patent with Athersys. V.B. reports research support from Incyte, Gamida Cell, and BMS; scientific advisory board membership for Gamida Cell, and Karyopharm; and participation on a data and safety monitoring board for Miltenyi Biotec. O.O.O. reports consultancy from Pfizer, Kite Pharma/Gilead, AbbVie, Janssen, TGR Therapeutics, Novartis, and Curio Science and institutional research funding from Kite Pharma/Gilead, Pfizer, and Daiichi Sankyo. B.R.D. reports institutional research funding from Takeda, Janssen, Angiocrine, Pfizer, Poseida, MEI, and Orcabio; consultancy/advisory board membership for Jazz, Gamida Cell, MJH BioScience, and Arivan Research. S.J.S. reports research funding from AbbVie, Adaptive Biotechnologies, Celgene, DTRM, Genentech, Roche, Juno Therapeutics, Merck, Novartis, Incyte, Pharmacyclics and TG Therapeutics; honoraria from Celgene and Novartis; consultancy for AstraZeneca, BeiGene, Celgene, Genentech, Genmab, Fate Therapeutics, Roche, Incyte, Juno Therapeutics, Legend Biotech, Loxo Oncology, Morphosys, Mustang Biotech, Nordic Nanovector, Novartis, and Regeneron; and patents related to CD19 CAR T cells and autologous costimulated T cells. M-A.P. reports honoraria from AbbVie, Astellas, Bristol-Myers Squibb, Celgene, Equilium, Incyte, Karyopharm, Kite Pharma/Gilead, Merck, Miltenyi Biotec, MorphoSys, Novartis, Nektar Therapeutics, Omeros, OrcaBio, Takeda, VectivBio AG, and Vor Biopharma; participation on a data and safety monitoring board for Cidara Therapeutics, Medigene, Sellas Life Sciences, and Servier and the scientific advisory board of NexImmune; ownership interests in NexImmune and Omeros; and research support for clinical trials from Incyte, Kite Pharma/Gilead, Miltenyi Biotec, and Novartis. M.R.B. reports membership on an advisory board or consultancy for Kite Pharma/Gilead, Novartis, CRISPR Therapeutics, Autolus Therapeutics, BMS, Incyte, Sana Biotechnology, and Iovance Biotherapeutics; serving on a speakers bureau for BMS, Kite/Gilead, Agios, and Incyte. D.L.P. reports honoraria for consulting or advisory board participation from Novartis, Kite Pharma/Gilead, Incyte, Gerson Lehrman Group, Janssen (Johnson & Johnson), Jazz, Adepcet Bio, DeCART, BMS, Bluebird Bio, and Kadmon; 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's former employer). The other authors report no conflicts of interest. Authorship statement: Conception and design: P.A.R. D.L.P. Collection and assembly of data: W-TH, JB, PAR Data analysis and interpretation: All authors. Manuscript writing: first draft, P.A.R. and D.L.P; revisions, all authors; final approval of manuscript, all authors. Financial disclosure: See Acknowledgments on page 675. Funding Information: Financial disclosure: This research was supported in part by a grant from Novartis Pharmaceuticals (to D.L.P.), National Cancer Institute Grant P30 CA008748 (to M.A.P.), and National Center for Advancing Translational Sciences Award UL1-TR002494 (to V.B.). M.P. was supported by an American-Italian Cancer Foundation Postdoctoral Research Fellowship and by the Associazione italiana contro le leucemie-linfomi e mieloma Milano e Provincia ONLUS. Publisher Copyright: © 2022 The American Society for Transplantation and Cellular Therapy

PY - 2022/10

Y1 - 2022/10

N2 - Axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) are CD19-directed chimeric antigen receptor (CAR) T cell therapies approved for the treatment of relapsed/refractory aggressive B cell lymphomas. We present a multicenter retrospective study among centers that prescribe either commercial product to evaluate usage patterns, safety and efficacy outcomes, and resource utilization. Data collection included all patients from 8 US centers who underwent apheresis between May 1, 2018, and July 31, 2019. Patient selection, toxicity management, and disease assessment followed institutional practices. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were graded according to American Society for Transplantation and Cellular Therapy consensus criteria, and tumor responses were assessed according to the Lugano 2014 classification scheme. A total of 260 patients underwent apheresis, including 168 (65%) for axi-cel and 92 (35%) for tisa-cel. Among the infused patients, the median age was 59 years for axi-cel recipients and 67 years for tisa-cel recipients (P < .001). The median time from apheresis to infusion was 28 days for axi-cel recipients and 45 days for tisa-cel recipients (P < .001). Sixty-one percent of the axi-cel recipients and 43% of the tisa-cel recipients would have been ineligible for the ZUMA-1 and JULIET trials, respectively. Grade ≥3 CRS occurred in 9% of axi-cel recipients and in 1% of tisa-cel recipients (P = .017), and grade ≥3 ICANS was seen in 38% of axi-cel recipients and 1% of tisa-cel recipients (P < .001). Inpatient cell therapy infusion was common (92% in axi-cel recipients, 37% in tisa-cel recipients). The day 90 overall response rate was 52% in the axi-cel group and 41% in the tisa-cel group (P =. 113), with complete response in 44% and 35%, respectively (P =. 319). Twelve-month progression-free survival (42% versus 32%; P =. 206) and overall survival (62% versus 59%; P =. 909) rates were comparable in the axi-cel and tisa-cel groups. Baseline characteristics differed between the 2 groups, although response rates and survival outcomes were comparable, albeit lower than those in the pivotal trials. Safety and resource utilization appear to be key differentiators between axi-cel and tisa-cel.

AB - Axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) are CD19-directed chimeric antigen receptor (CAR) T cell therapies approved for the treatment of relapsed/refractory aggressive B cell lymphomas. We present a multicenter retrospective study among centers that prescribe either commercial product to evaluate usage patterns, safety and efficacy outcomes, and resource utilization. Data collection included all patients from 8 US centers who underwent apheresis between May 1, 2018, and July 31, 2019. Patient selection, toxicity management, and disease assessment followed institutional practices. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were graded according to American Society for Transplantation and Cellular Therapy consensus criteria, and tumor responses were assessed according to the Lugano 2014 classification scheme. A total of 260 patients underwent apheresis, including 168 (65%) for axi-cel and 92 (35%) for tisa-cel. Among the infused patients, the median age was 59 years for axi-cel recipients and 67 years for tisa-cel recipients (P < .001). The median time from apheresis to infusion was 28 days for axi-cel recipients and 45 days for tisa-cel recipients (P < .001). Sixty-one percent of the axi-cel recipients and 43% of the tisa-cel recipients would have been ineligible for the ZUMA-1 and JULIET trials, respectively. Grade ≥3 CRS occurred in 9% of axi-cel recipients and in 1% of tisa-cel recipients (P = .017), and grade ≥3 ICANS was seen in 38% of axi-cel recipients and 1% of tisa-cel recipients (P < .001). Inpatient cell therapy infusion was common (92% in axi-cel recipients, 37% in tisa-cel recipients). The day 90 overall response rate was 52% in the axi-cel group and 41% in the tisa-cel group (P =. 113), with complete response in 44% and 35%, respectively (P =. 319). Twelve-month progression-free survival (42% versus 32%; P =. 206) and overall survival (62% versus 59%; P =. 909) rates were comparable in the axi-cel and tisa-cel groups. Baseline characteristics differed between the 2 groups, although response rates and survival outcomes were comparable, albeit lower than those in the pivotal trials. Safety and resource utilization appear to be key differentiators between axi-cel and tisa-cel.

KW - Aggressive large B cell lymphoma

KW - CAR T cell therapy outcomes

KW - CAR T cell toxicity

KW - Chimeric antigen receptor T cell therapy

KW - Resource utilization

UR - http://www.scopus.com/inward/record.url?scp=85136273493&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85136273493&partnerID=8YFLogxK

U2 - 10.1016/j.jtct.2022.07.011

DO - 10.1016/j.jtct.2022.07.011

M3 - Article

C2 - 35850429

AN - SCOPUS:85136273493

SN - 2666-6367

VL - 28

SP - 669

EP - 676

JO - Transplantation and Cellular Therapy

JF - Transplantation and Cellular Therapy

IS - 10

ER -

Patterns of Use, Outcomes, and Resource Utilization among Recipients of Commercial Axicabtagene Ciloleucel and Tisagenlecleucel for Relapsed/Refractory Aggressive B Cell Lymphomas

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