TY - JOUR
T1 - Impact of CD19 CAR T-cell product type on outcomes in relapsed or refractory aggressive B-NHL
AU - Gauthier, Jordan
AU - Gazeau, Nicolas
AU - Hirayama, Alexandre V.
AU - Hill, Joshua A.
AU - Wu, Vicky
AU - Cearley, Aisling
AU - Perkins, Paula
AU - Kirk, Angela
AU - Shadman, Mazyar
AU - Chow, Victor A.
AU - Gopal, Ajay K.
AU - Hodges Dwinal, Alexandria
AU - Williamson, Staci
AU - Myers, Jessie
AU - Chen, Andy
AU - Nagle, Sarah
AU - Hayes-Lattin, Brandon
AU - Schachter, Levanto
AU - Maloney, David G.
AU - Turtle, Cameron J.
AU - Sorror, Mohamed L.
AU - Maziarz, Richard T.
N1 - Funding Information:
Conflict-of-interest disclosure: J.G. reports honoraria from Larvol, Eusapharma, JMP, Multerra Bio; research support from Juno Therapeutics, a Bristol Myers Squibb company, and Sobi; and participation in an advisory board for JNJ/Legend Biotech. A.V.H. reports honoraria from Bristol Myers Squibb and Novartis and research support from Juno Therapeutics, a Bristol Myers Squibb company. A. Chen has participated in advisory board meetings for Morphosys, Mesoblast, and Fate Therapeutics. J.A.H. has served as a consultant for Allogene and Gilead, with research support from Gilead. S.N. is employed by Novartis. V.A.C. has received research funding from AstraZeneca. D.G.M. has received research funding paid to his institution and honoraria from Juno Therapeutics, a BMS Company, Celgene, a BMS Company, and Kite Pharma; has participated in ad hoc advisory board meetings and received honoraria from Amgen, BMS, Genentech, Gilead Sciences, Incyte, Janssen, Legend Biotech, Mustang Bio, MorphoSys, Novartis, Pharmacyclics, and Umoja; has rights to royalties from Fred Hutch for patents licensed to Juno/BMS; and is a member of the A2 Biotherapeutics Scientific Advisory Board with stock options and compensation and is a member of the Navan Technologies Scientific Advisory Board with stock options and compensation. C.J.T. receives research funding from Juno Therapeutics/BMS and Nektar Therapeutics; serves on Scientific Advisory Boards for Precision Biosciences, Eureka Therapeutics, Caribou Biosciences, T-CURX, Myeloid Therapeutics, ArsenalBio, and Century Therapeutics; has stock/options in Precision Biosciences, Eureka Therapeutics, Caribou Biosciences, Myeloid Therapeutics, and ArsenalBio; has the right to receive royalties from Fred Hutch as an inventor on patents related to CAR T-cell therapy that are licensed to Juno Therapeutics/BMS; and served on ad hoc advisory boards (last 12 months) for GlaxoSmithKline. M.L.S. is a member of consulting, advisory boards, steering committees, or data safety monitoring committees: Abbvie, Genentech, AstraZeneca, Sound Biologics, Pharmacyclics, Beigene, Bristol Myers Squibb, Morphosys/Incyte, TG Therapeutics, Innate Pharma, Kite Pharma, Adaptive Biotechnologies, Epizyme, Eli Lilly, Adaptimmune, Mustang Bio, Regeneron, Merck, Fate Therapeutics, MEI Pharma, and Atara Biotherapeutics; Research funding: Mustang Bio, Celgene, Bristol Myers Squibb, Pharmacyclics, Gilead, Genentech, AbbVie, TG Therapeutics, Beigene, AstraZeneca, Sunesis, Atara Biotherapeutics, Genmab, and Morphosys/Incyte. R.T.M. is an advisor or consultant for AlloVir, Artiva, CRISPR Therapeutics, CytoDyn, Incyte, and Novartis; reports honoraria from Bristol-Myers Squibb/Celgene, Incyte, Intellia, Kite, Omeros, Orca BioSystems, and PACT Pharma; research support from BMS/Celgene/Juno and Novartis; participation in a data and safety monitoring board for Athersys, Novartis, and Vor Pharmaceutical; and holds a patent with Athersys. The remaining authors declare no competing financial interests.
Funding Information:
The authors thank both the Fred Hutchinson Cancer Research Center Cell Processing Facility and Seattle Cancer Care Alliance Cell Therapy Laboratory, the staff of the Program in Immunology and Seattle Cancer Care Alliance Immunotherapy Clinic, and the Oregon Health and Science University Cell Therapy Clinical, Administrative, and Laboratory Programs. J.G. thanks the National Institutes of Health/National Cancer Institute Cancer Center Support Grant (P30 CA015704-45).
Funding Information:
J.G. thanks the National Institutes of Health/National Cancer Institute Cancer Center Support Grant (P30 CA015704-45).
Publisher Copyright:
© 2022 American Society of Hematology
PY - 2022/6/30
Y1 - 2022/6/30
N2 - CD19-targeted chimeric antigen receptor-engineered (CD19 CAR) T cells are novel therapies showing great promise for patients with relapsed or refractory (R/R) aggressive B-cell non-Hodgkin lymphoma (B-NHL). Single-arm studies showed significant variations in outcomes across distinct CD19 CAR T-cell products. To estimate the independent impact of the CAR T-cell product type on outcomes, we retrospectively analyzed data from 129 patients with R/R aggressive B-NHL treated with cyclophosphamide and fludarabine lymphodepletion followed by either a commercially available CD19 CAR T-cell therapy (axicabtagene ciloleucel [axicel] or tisagenlecleucel [tisacel]), or the investigational product JCAR014 on a phase 1/2 clinical trial (NCT01865617). After adjustment for age, hematopoietic cell transplantation-specific comorbidity index, lactate dehydrogenase (LDH), largest lesion diameter, and absolute lymphocyte count (ALC), CAR T-cell product type remained associated with outcomes in multivariable models. JCAR014 was independently associated with lower cytokine release syndrome (CRS) severity compared with axicel (adjusted odds ratio [aOR], 0.19; 95% confidence interval [CI]; 0.08-0.46), with a trend toward lower CRS severity with tisacel compared with axicel (aOR, 0.47; 95% CI, 0.21-1.06; P =.07). Tisacel (aOR, 0.17; 95% CI, 0.06-0.48) and JCAR014 (aOR, 0.17; 95% CI, 0.06-0.47) were both associated with lower immune effector cell-associated neurotoxicity syndrome severity compared with axicel. Lower odds of complete response (CR) were predicted with tisacel and JCAR014 compared with axicel. Although sensitivity analyses using either positron emission tomography- or computed tomography-based response criteria also suggested higher efficacy of axicel over JCAR014, the impact of tisacel vs axicel became undetermined. Higher preleukapheresis LDH, largest lesion diameter, and lower ALC were independently associated with lower odds of CR. We conclude that CD19 CAR T-cell product type independently impacts toxicity and efficacy in R/R aggressive B-NHL patients.
AB - CD19-targeted chimeric antigen receptor-engineered (CD19 CAR) T cells are novel therapies showing great promise for patients with relapsed or refractory (R/R) aggressive B-cell non-Hodgkin lymphoma (B-NHL). Single-arm studies showed significant variations in outcomes across distinct CD19 CAR T-cell products. To estimate the independent impact of the CAR T-cell product type on outcomes, we retrospectively analyzed data from 129 patients with R/R aggressive B-NHL treated with cyclophosphamide and fludarabine lymphodepletion followed by either a commercially available CD19 CAR T-cell therapy (axicabtagene ciloleucel [axicel] or tisagenlecleucel [tisacel]), or the investigational product JCAR014 on a phase 1/2 clinical trial (NCT01865617). After adjustment for age, hematopoietic cell transplantation-specific comorbidity index, lactate dehydrogenase (LDH), largest lesion diameter, and absolute lymphocyte count (ALC), CAR T-cell product type remained associated with outcomes in multivariable models. JCAR014 was independently associated with lower cytokine release syndrome (CRS) severity compared with axicel (adjusted odds ratio [aOR], 0.19; 95% confidence interval [CI]; 0.08-0.46), with a trend toward lower CRS severity with tisacel compared with axicel (aOR, 0.47; 95% CI, 0.21-1.06; P =.07). Tisacel (aOR, 0.17; 95% CI, 0.06-0.48) and JCAR014 (aOR, 0.17; 95% CI, 0.06-0.47) were both associated with lower immune effector cell-associated neurotoxicity syndrome severity compared with axicel. Lower odds of complete response (CR) were predicted with tisacel and JCAR014 compared with axicel. Although sensitivity analyses using either positron emission tomography- or computed tomography-based response criteria also suggested higher efficacy of axicel over JCAR014, the impact of tisacel vs axicel became undetermined. Higher preleukapheresis LDH, largest lesion diameter, and lower ALC were independently associated with lower odds of CR. We conclude that CD19 CAR T-cell product type independently impacts toxicity and efficacy in R/R aggressive B-NHL patients.
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UR - http://www.scopus.com/inward/citedby.url?scp=85133153646&partnerID=8YFLogxK
U2 - 10.1182/blood.2021014497
DO - 10.1182/blood.2021014497
M3 - Article
C2 - 35439295
AN - SCOPUS:85133153646
SN - 0006-4971
VL - 139
SP - 3722
EP - 3731
JO - Blood
JF - Blood
IS - 26
ER -