Efficacy and safety of bendamustine for lymphodepletion before lisocabtagene maraleucel.
Bbendamustine
Ccytokine-release syndrome (CRS)
Chimeric antigen receptor T cells (CART)
Immune effector cell associated neurotoxicity syndrome (ICANS)
Lisocabtagene maraleucel
Lymphodepletion
Non-Hodgkin lymphoma (NHL)
Toxicities
Journal
Journal of hematology & oncology
ISSN: 1756-8722
Titre abrégé: J Hematol Oncol
Pays: England
ID NLM: 101468937
Informations de publication
Date de publication:
22 Apr 2024
22 Apr 2024
Historique:
received:
29
01
2024
accepted:
04
04
2024
medline:
22
4
2024
pubmed:
22
4
2024
entrez:
21
4
2024
Statut:
epublish
Résumé
Bendamustine has been retrospectively shown to be an effective and safe lymphodepletion regimen prior to the anti-CD19 chimeric antigen receptor T cell (CART) products tisagenlecleucel and axicabtagene ciloleucel, as well as the anti-BCMA CART products idecabtagene vicleucel and ciltacabtagene autoleucel. However, bendamustine as lymphodepletion prior to lisocabtagene maraleucel (liso-cel), a 4-1BB co-stimulated, fixed CD4:CD8 ratio anti-CD19 CART product, has not been described yet. Thus, we studied a cohort of sequentially-treated patients with large B-cell lymphomas who received bendamustine lymphodepletion before liso-cel at the University of Pennsylvania between 5/2021 and 12/2023 (n = 31). Patients were evaluated for toxicities and responses. Of note, 7 patients (22.6%) would have dnot met the inclusion criteria for the registrational liso-cel clinical trials, mostly due to older age. Overall and complete response rates were 76.9% and 73.1%, respectively. At a median follow-up of 6.3 months, the 6-month progression-free and overall survival were 59.9% and 91.1%, respectively. Rates of cytokine-release syndrome (CRS) and neurotoxicity (ICANS) of any grade were 9.7% and 9.7%, respectively, with no grade ≥ 3 events. No infections were reported during the first 30 days following liso-cel infusion. Neutropenia ≥ grade 3 was observed in 29.0% of patients; thrombocytopenia ≥ grade 3 occurred in 9.7%. In conclusion, bendamustine lymphodepletion before liso-cel appears to be a strategy that can drive tumor responses while ensuring a mild toxicity profile.
Identifiants
pubmed: 38644469
doi: 10.1186/s13045-024-01542-9
pii: 10.1186/s13045-024-01542-9
doi:
Types de publication
Letter
Langues
eng
Sous-ensembles de citation
IM
Pagination
19Subventions
Organisme : NIH HHS
ID : P01 PCA214278C
Pays : United States
Informations de copyright
© 2024. The Author(s).
Références
Ghilardi G, Braendstrup P, Chong EA, Schuster SJ, Svoboda J, Ruella M. CAR-T TREK through the lymphoma universe, to boldly go where no other therapy has gone before. Br J Haematol. 2020.
Hirayama AV, Gauthier J, Hay KA, Voutsinas JM, Wu Q, Gooley T, et al. The response to lymphodepletion impacts PFS in patients with aggressive non-hodgkin lymphoma treated with CD19 CAR T cells. Blood. 2019;133(17):1876–87.
doi: 10.1182/blood-2018-11-887067
pubmed: 30782611
pmcid: 6484391
Abramson JS, Palomba ML, Gordon LI, Lunning MA, Wang M, Arnason J, et al. Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): a multicentre seamless design study. Lancet. 2020;396(10254):839–52.
doi: 10.1016/S0140-6736(20)31366-0
pubmed: 32888407
Abramson JS, Palomba ML, Gordon LI, Lunning MA, Wang ML, Arnason JE et al. Two-year follow-up of lisocabtagene maraleucel in relapsed or refractory large B-cell lymphoma in TRANSCEND NHL 001. Blood. 2023.
Abramson JS, Solomon SR, Arnason J, Johnston PB, Glass B, Bachanova V, et al. Lisocabtagene maraleucel as second-line therapy for large B-cell lymphoma: primary analysis of the phase 3 TRANSFORM study. Blood. 2023;141(14):1675–84.
doi: 10.1182/blood.2022018730
pubmed: 36542826
Ghilardi G, Chong EA, Svoboda J, Wohlfarth P, Nasta SD, Williamson S, et al. Bendamustine is safe and effective for lymphodepletion before tisagenlecleucel in patients with refractory or relapsed large B-cell lymphomas. Ann Oncol. 2022;33(9):916–28.
doi: 10.1016/j.annonc.2022.05.521
pubmed: 35690221
Schuster SJ, Bishop MR, Tam CS, Waller EK, Borchmann P, McGuirk JP, et al. Tisagenlecleucel in adult relapsed or refractory diffuse large B-Cell lymphoma. N Engl J Med. 2019;380(1):45–56.
doi: 10.1056/NEJMoa1804980
pubmed: 30501490
Ong SY, Pak S, Mei M, Wang Y, Popplewell L, Baird JH, et al. Bendamustine lymphodepletion is a well-tolerated alternative to fludarabine and cyclophosphamide lymphodepletion for axicabtagene ciloleucel therapy for aggressive B-cell lymphoma. Am J Hematol. 2023;98(11):1751–61.
doi: 10.1002/ajh.27069
pubmed: 37668287
Ghilardi G, Paruzzo L, Svoboda J, Chong EA, Shestov AA, Chen L, et al. Bendamustine lymphodepletion before axicabtagene ciloleucel is safe and associates with reduced inflammatory cytokines. Blood Adv. 2024;8(3):653–66.
doi: 10.1182/bloodadvances.2023011492
pubmed: 38113468
Maziarz RT, Diaz A, Miklos DB, Shah NN. Perspective: an International Fludarabine shortage: supply chain issues impacting transplantation and Immune Effector Cell Therapy Delivery. Transpl Cell Ther. 2022;28(11):723–6.
doi: 10.1016/j.jtct.2022.08.002
Pennisi M, Jain T, Santomasso BD, Mead E, Wudhikarn K, Silverberg ML, et al. Comparing CAR T-cell toxicity grading systems: application of the ASTCT grading system and implications for management. Blood Adv. 2020;4(4):676–86.
doi: 10.1182/bloodadvances.2019000952
pubmed: 32084260
pmcid: 7042979
Sidana S, Hosoya H, Jensen A, Liu L, Goyal A, Hovanky V, et al. Bendamustine vs. fludarabine/cyclophosphamide lymphodepletion prior to BCMA CAR-T cell therapy in multiple myeloma. Blood Cancer J. 2023;13(1):158.
doi: 10.1038/s41408-023-00929-0
pubmed: 37833271
pmcid: 10576036