PMID- 36878427 OWN - NLM STAT- MEDLINE DCOM- 20230605 LR - 20230608 IS - 2666-6367 (Electronic) IS - 2666-6367 (Linking) VI - 29 IP - 6 DP - 2023 Jun TI - Outcomes of CD19-Directed Chimeric Antigen Receptor T Cell Therapy for Transformed Nonfollicular Lymphoma. PG - 349.e1-349.e8 LID - S2666-6367(23)01131-4 [pii] LID - 10.1016/j.jtct.2023.02.021 [doi] AB - CD19-directed chimeric antigen receptor (CAR) T cell (CAR-T) therapy with axicabtagene ciloleucel (axi-cel) or tisagenlecleucel (tisa-cel) are approved for the treatment of relapsed or refractory large B cell lymphoma (LBCL), including de novo diffuse LBCL (DLBCL), primary mediastinal B cell lymphoma (PMBCL), and transformed follicular lymphoma (tFL). Transformed nonfollicular lymphomas (tNFLs), including transformed marginal zone lymphoma (tMZL) and transformed chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) were not included in their respective pivotal studies. This study was conducted to evaluate the outcomes of axi-cel and tisa-cel in tNFL patients, including those who received ibrutinib concomitantly through apheresis, lymphodepletion, and CAR-T infusion. This single-center retrospective study included all patients with tCLL/SLL, tMZL, tFL, and DLBCL/PMBCL treated with CAR-T therapy outside of a clinical trial setting from November 2017 to May 2021 at Moffitt Cancer Center, Tampa, Florida. We analyzed and compared outcomes in patients with tCLL/SLL or tMZL and patients with DLBCL/tFL. The study included 134 patients who received a total of 136 CAR-T treatments (111 with axi-cel and 25 with tisa-cel). Ninety patients had de novo DLBCL/PMBCL, 23 had tFL, and 21 had tNFL (12 with tMZL and 9 with tCLL/SLL). The overall response and complete response rates were 66.7% and 55.6%, respectively, for tCLL/SLL and 92.9% and 71.4% for tMZL. The overall response and complete response rates were not different between tNFL and DLBCL/tFL (P = .92 and .81, respectively). At a median follow-up of 21.3 months, the median progression-free survival (PFS) for tCLL/SLL was 5.4 months (95% confidence interval [CI], .8 month to not assessable [NA]); for tMZL, the median PFS was not reached (NR) (95% CI, 2.3 months to NA); and for DLBCL/tFL, the median PFS was 14.3 months (95% CI, 5.6 months to NA) (P = .58). The estimated 1-year PFS rate was 29.6% (95% CI, 5.2% to 60.7%) for tCLL/SLL, 50.0% (95% CI, 22.9% to 72.2%) for tMZL, 42.7% (95% CI, 22.4% to 61.6%) for tNFL, and 53.0% (95% CI, 42.3% to 62.5%) for DLBCL/tFL. The median overall survival was NR (95% CI, 9.2 months to NA) for tCLL/SLL, 27.1 months (95% CI, 8.5 months to NA) for tMZL, and NR (95% CI, 17.4 months to NA) for DLBCL/tFL (P = .79). Compared to the DLBCL/tFL cohort, tNFL patients were more likely to develop immune effector cell-associated neurologic syndrome (ICANS) and to receive tocilizumab (P = .04 and .01, respectively, after controlling for CAR-T product) and with a possibly higher incidence of grade >/=3 cytokine release syndrome (CRS) (P = .07). Two patients in the tNFL cohort died of treatment-related toxicity after receiving axi-cel. Six tNFL patients received ibrutinib concurrently with tisa-cel, with 1 case of grade >/=3 CRS/ICANS that rapidly resolved and no other severe toxicities. Our case series supports the use of CD19 CAR-T therapy in relapsed/refractory tCLL/SLL and tMZL. The concurrent use of ibrutinib and tisa-cel in tNFL was associated with manageable toxicity in tNFL. CI - Copyright (c) 2023 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved. FAU - Dong, Ning AU - Dong N AD - Malignant Hematology, Moffitt Cancer Center, Tampa, Florida. FAU - Rubio Lopes-Garcia, Lucia AU - Rubio Lopes-Garcia L AD - Hematology and Oncology, Hospital Universitario Doctor Peset, Valencia, Spain. FAU - Vinal, David AU - Vinal D AD - Medical Oncology, Hospital Universitario La Paz, Madrid, Spain. FAU - Bachmeier, Christina AU - Bachmeier C AD - Blood and Marrow Transplant and Cellular Immunotherapy, Moffitt Cancer Center, Tampa, Florida. FAU - Shah, Bijal D AU - Shah BD AD - Malignant Hematology, Moffitt Cancer Center, Tampa, Florida. FAU - Nishihori, Taiga AU - Nishihori T AD - Blood and Marrow Transplant and Cellular Immunotherapy, Moffitt Cancer Center, Tampa, Florida. FAU - Khimani, Farhad AU - Khimani F AD - Blood and Marrow Transplant and Cellular Immunotherapy, Moffitt Cancer Center, Tampa, Florida. FAU - Davila, Marco L AU - Davila ML AD - Roswell Park Cancer Institute, Buffalo, New York. FAU - Lazaryan, Aleksandr AU - Lazaryan A AD - Blood and Marrow Transplant and Cellular Immunotherapy, Moffitt Cancer Center, Tampa, Florida. FAU - Pinilla-Ibarz, Javier AU - Pinilla-Ibarz J AD - Malignant Hematology, Moffitt Cancer Center, Tampa, Florida. FAU - Locke, Frederick L AU - Locke FL AD - Blood and Marrow Transplant and Cellular Immunotherapy, Moffitt Cancer Center, Tampa, Florida. FAU - Jain, Michael D AU - Jain MD AD - Blood and Marrow Transplant and Cellular Immunotherapy, Moffitt Cancer Center, Tampa, Florida. FAU - Chavez, Julio C AU - Chavez JC AD - Malignant Hematology, Moffitt Cancer Center, Tampa, Florida. Electronic address: julio.c.chavez@moffitt.org. LA - eng PT - Journal Article DEP - 20230305 PL - United States TA - Transplant Cell Ther JT - Transplantation and cellular therapy JID - 101774629 RN - 0 (Receptors, Chimeric Antigen) SB - IM MH - Humans MH - *Receptors, Chimeric Antigen/therapeutic use MH - Retrospective Studies MH - *Lymphoma, Large B-Cell, Diffuse/therapy MH - *Lymphoma, Follicular/therapy MH - *Lymphoma, B-Cell, Marginal Zone MH - Cell- and Tissue-Based Therapy OTO - NOTNLM OT - Chimeric antigen receptor T cell therapy OT - Ibrutinib OT - Outcome OT - Transformed chronic lymphocytic leukemia OT - Transformed marginal-zone lymphoma EDAT- 2023/03/07 06:00 MHDA- 2023/06/05 06:42 CRDT- 2023/03/06 19:26 PHST- 2022/12/10 00:00 [received] PHST- 2023/02/01 00:00 [revised] PHST- 2023/02/27 00:00 [accepted] PHST- 2023/06/05 06:42 [medline] PHST- 2023/03/07 06:00 [pubmed] PHST- 2023/03/06 19:26 [entrez] AID - S2666-6367(23)01131-4 [pii] AID - 10.1016/j.jtct.2023.02.021 [doi] PST - ppublish SO - Transplant Cell Ther. 2023 Jun;29(6):349.e1-349.e8. doi: 10.1016/j.jtct.2023.02.021. Epub 2023 Mar 5.