TY - JOUR
T1 - Allogeneic transplant and CAR-T therapy after autologous transplant failure in DLBCL
T2 - A noncomparative cohort analysis
AU - Hamadani, Mehdi
AU - Gopal, Ajay K.
AU - Pasquini, Marcelo
AU - Kim, Soyoung
AU - Qiu, Xianmiao
AU - Ahmed, Sairah
AU - Lazaryan, Aleksandr
AU - Raj Bhatt, Vijaya
AU - Daly, Andrew
AU - Lulla, Premal
AU - Ciurea, Stefan
AU - Gauthier, Jordan
AU - Agrawal, Vaibhav
AU - Grover, Natalie S.
AU - Lekakis, Lazaros
AU - Modi, Dipenkumar
AU - Dahi, Parastoo B.
AU - Herr, Megan M.
AU - Connor Johnson, P.
AU - Hashmi, Hamza
AU - Hematti, Peiman
AU - Locke, Frederick L.
N1 - Funding Information:
Conflict-of-interest disclosure: M.H. received research support/ funding from Takeda Pharmaceutical Company, Spectrum Pharmaceuticals, and Astellas Pharma; consulted for Janssen, Incyte Corporation, ADC Therapeutics, Celgene Corporation, Omeros, Verastem, and MorphoSys; and was on the speaker’s bureau for Sanofi Gen-zyme, AstraZeneca, and BeiGene. A.K.G. received research funding from Bristol Myers Squibb, Pharmacyclics, Gilead, Genentech, Astra-Zeneca, Pfizer, Teva, Takeda, Acrotec, IgM, I-Mab, Agios, and Merck and consulted for Abbvie, Genentech, Janssen, AstraZeneca, Phar-macyclics, Bristol Myers Squibb, Amgen, Morphosys, TG Therapeutics, Kite Pharma, Adaptive, SeaGen, Epizyme, Gilead, ADCT, Incyte, Karyopharm, Actinium, Asana bio, Nurix, and Aptevo. F.L.L. was a scientific advisor for Allogene, Amgen, Bluebird Bio, BMS/Celgene, Cal-ibr, Cellular Biomedicine Group, GammaDelta Therapeutics, Iovance, Kite Pharma, Janssen, Legend Biotech, Novartis, Wugen, and Umoja; received research funding from Kite Pharma (institutional), Allogene (institutional), Novartis (institutional); and holds several patents (held by the institution in his name; unlicensed) in the field of cellular immunotherapy. S.C. was a scientific advisor for Allogene, Acrotech, Cellularity, CareDx, Kiadis Pharma, Milteniy Biotech, and Molmed and received research funding from Miltenyi and Kiadis Pharma. P.B.D. sat on an advisory board for Kite (Gilead). J.G. received institutional research support from CCSG and SCCA Swim Across America and received consulting fees from JMP, Eusapharma, Larvol, and Multerra Bio. The remaining authors declare no competing financial interests.
Funding Information:
The CIBMTR is supported primarily by Public Health Service grant U24CA076518 from the National Cancer Institute (NCI), the National Heart, Lung and Blood Institute, and the National Institute of Allergy and Infectious Diseases, grant U24CA233032 from the NCI, grant HHSH250201700006C from the Health Resources and Services Administration, and grants N00014-20-1-2705 and N00014-20-1-2832 from the Office of Naval Research. Support is also provided by Be the Match Foundation, the Medical College of Wisconsin, the National Marrow Donor Program, and the following commercial entities: AbbVie, Accenture, Actinium Pharmaceuticals, Inc., Adaptive Biotechnologies Corporation, Adienne SA, Allovir, Inc., Amgen, Inc., Astellas Pharma US, bluebird bio, inc., Bristol Myers Squibb Co., CareDx, CSL Behring, CytoSen Therapeutics, Inc., Daiichi Sankyo Co., Ltd., Eurofins Viracor, ExcellThera, Fate Therapeutics, Gamida-Cell, Ltd., Genentech Inc, Gilead, GlaxoS-mithKline, Incyte Corporation, Janssen/Johnson & Johnson, Jasper Therapeutics, Jazz Pharmaceuticals, Inc., Karyopharm Therapeutics, Kiadis Pharma, Kite, a Gilead Company, Kyowa Kirin, Magenta Therapeutics, Medac GmbH, Merck & Co., Millennium, the Takeda Oncology Co., Miltenyi Biotec, Inc., MorphoSys, Novartis Pharmaceuticals Corporation, Omeros Corporation, Oncopeptides, Inc., Orca Biosystems, Inc., Pfizer, Inc., Pharmacyclics, LLC, Sanofi Gen-zyme, Seagen, Inc., Stemcyte, Takeda Pharmaceuticals, Tscan, Vertex, Vor Biopharma, and Xenikos BV.
Publisher Copyright:
© 2022 American Society of Hematology. All rights reserved.
PY - 2022/1/25
Y1 - 2022/1/25
N2 - Allogeneic transplant (alloHCT) and chimeric antigen receptor modified (CAR)-T cell therapy are potentially cuarative options of diffuse large B-cell lymphoma (DLBCL) relapsing after an autologous (auto)HCT. Although the Center for International Blood and Marrow Transplant Research (CIBMTR) prognostic model can predict outcomes of alloHCT in DLBCL after autoHCT failure, corresponding models of CAR-T treatment in similar patient populations are not available. In this noncomparative registry analysis, we report outcomes of patients with DLBCL ($18 years) undergoing a reduced intensity alloHCT or CAR-T therapy with axicabtagene ciloleucel during 2012 to 2019 after a prior auto-HCT failure and apply the CIBMTR prognostic model to CAR-T recipients. A total of 584 patients were included. The 1-year relapse, nonrelapse mortality, overall survival (OS), and progression-free survival for CAR-T treatment after autoHCT failure were 39.5%, 4.8%, 73.4%, and 55.7%, respectively. The corresponding rates in the alloHCT cohort were 26.2%, 20.0%, 65.6%, and 53.8%, respectively. The 1-year OS of alloHCT recipients classified as low-, intermediate- and high/very high-risk groups according to the CIBMTR prognostic score was 73.3%, 59.9%, and 46.3%, respectively (P = .002). The corresponding rates for low-, intermediate-, and high/very high-risk CAR-T patients were 88.4%, 76.4%, and 52.8%, respectively (P <.001). This registry analysis shows that both CAR-T and alloHCT can provide durable remissions in a subset of patients with DLBCL relapsing after a prior autoHCT. The simple CIBMTR prognostic score can be used to identify patients at high risk of treatment failure after either procedure. Evaluation of novel relapse mitigations strategies after cellular immunotherapies are warranted in these high-risk patients.
AB - Allogeneic transplant (alloHCT) and chimeric antigen receptor modified (CAR)-T cell therapy are potentially cuarative options of diffuse large B-cell lymphoma (DLBCL) relapsing after an autologous (auto)HCT. Although the Center for International Blood and Marrow Transplant Research (CIBMTR) prognostic model can predict outcomes of alloHCT in DLBCL after autoHCT failure, corresponding models of CAR-T treatment in similar patient populations are not available. In this noncomparative registry analysis, we report outcomes of patients with DLBCL ($18 years) undergoing a reduced intensity alloHCT or CAR-T therapy with axicabtagene ciloleucel during 2012 to 2019 after a prior auto-HCT failure and apply the CIBMTR prognostic model to CAR-T recipients. A total of 584 patients were included. The 1-year relapse, nonrelapse mortality, overall survival (OS), and progression-free survival for CAR-T treatment after autoHCT failure were 39.5%, 4.8%, 73.4%, and 55.7%, respectively. The corresponding rates in the alloHCT cohort were 26.2%, 20.0%, 65.6%, and 53.8%, respectively. The 1-year OS of alloHCT recipients classified as low-, intermediate- and high/very high-risk groups according to the CIBMTR prognostic score was 73.3%, 59.9%, and 46.3%, respectively (P = .002). The corresponding rates for low-, intermediate-, and high/very high-risk CAR-T patients were 88.4%, 76.4%, and 52.8%, respectively (P <.001). This registry analysis shows that both CAR-T and alloHCT can provide durable remissions in a subset of patients with DLBCL relapsing after a prior autoHCT. The simple CIBMTR prognostic score can be used to identify patients at high risk of treatment failure after either procedure. Evaluation of novel relapse mitigations strategies after cellular immunotherapies are warranted in these high-risk patients.
UR - http://www.scopus.com/inward/record.url?scp=85123544420&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85123544420&partnerID=8YFLogxK
U2 - 10.1182/bloodadvances.2021005788
DO - 10.1182/bloodadvances.2021005788
M3 - Article
C2 - 34673903
AN - SCOPUS:85123544420
VL - 6
SP - 486
EP - 494
JO - Blood advances
JF - Blood advances
SN - 2473-9529
IS - 2
ER -