Anti-CD19 chimeric antigen receptor T-cell therapy has less efficacy in Richter transformation than in de novo large B-cell lymphoma and transformed low-grade B-cell lymphoma Journal Article
| Authors: | Benjamini, O.; Fried, S.; Shouval, R.; Flynn, J. R.; Beyar-Katz, O.; Leslie, L. A.; Zuckerman, T.; Yerushalmi, R.; Shem-Tov, N.; Palomba, M. L.; Danylesko, I.; Sdayoor, I.; Malka, H.; Itzhaki, O.; Suh, H.; Devlin, S. M.; Marcus, R.; Dahi, P. B.; Jacoby, E.; Shah, G. L.; Sauter, C. S.; Ip, A.; Perales, M. A.; Nagler, A.; Shimoni, A.; Scordo, M.; Avigdor, A. |
| Article Title: | Anti-CD19 chimeric antigen receptor T-cell therapy has less efficacy in Richter transformation than in de novo large B-cell lymphoma and transformed low-grade B-cell lymphoma |
| Abstract: | The activity of anti-CD19 chimerci antigen receptor (CAR) T-cell therapy in chronic lymphocytic leukemia (CLL) with Richter’s transformation (RT) to aggressive large B-cell lymphoma (LBCL) is largely unknown. In a multicenter retrospective study, we report the safety and efficacy of CAR T-cell therapy in patients with RT (N=30) compared to patients with aggressive B-cell lymphoma (N=283) and patients with transformed indolent non-Hodgkin lymphoma (iNHL) (N=141) between April 2016 and January 2023. Two-thirds of patients received prior therapy for CLL before RT and 89% of them received B-cell receptor and B-cell lymphoma 2 inhibitors. Toxicities of CAR T-cell therapy in RT were similar to other lymphomas, with no fatalities related to cytokine release syndrome or immune effector-cell associated neurotoxicity synderome. The 100-day overall response rate and complete response rates in patients with RT were 57% and 47%, respectively. With a median follow-up of 19 months, the median overall survival (OS) was 9.9 months in patients with RT compared to 18 months in de novo LBCL and not reached in patients with transformed iNHL. The OS at 12 months was 45% in patients with RT compared with 62% and 75% in patients with de novo LBCL and transformed iNHL, respectively. In a multivariate analysis, worse OS was associated with RT histology, elevated lactate dehydrogenase, and more prior lines of therapy. CAR T-cell therapy can salvage a proportion of patients with CLL and RT exposed to prior targeted agents; however, efficacy in RT is inferior compared to de novo LBCL and transformed iNHL. ©2024 Ferrata Storti Foundation. |
| Keywords: | adult; human tissue; treatment outcome; aged; aged, 80 and over; middle aged; retrospective studies; gene mutation; major clinical study; overall survival; fludarabine; lenalidomide; clinical trial; mortality; neutropenia; rituximab; neurotoxicity; follow up; cancer grading; protein bcl 2; progression free survival; thrombocytopenia; bendamustine; cyclophosphamide; steroid; retrospective study; protein p53; histology; b cell lymphoma; immunology; fluorescence in situ hybridization; karnofsky performance status; proportional hazards model; multicenter study; chimeric antigen receptor; lactate dehydrogenase; multivariate analysis; lymphoma, large b-cell, diffuse; chronic lymphatic leukemia; immunoglobulin deficiency; karyotype; follicular lymphoma; marginal zone lymphoma; therapy; adoptive immunotherapy; immunotherapy, adoptive; cd19 antigen; antigens, cd19; leukemia, lymphocytic, chronic, b-cell; non-hodgkin lymphoma; pathological complete response; adverse event; leukapheresis; apheresis; clinical outcome; cytokine release syndrome; b lymphocyte receptor; procedures; overall response rate; diffuse large b cell lymphoma; chemoimmunotherapy; tocilizumab; neoplasm grading; richter syndrome; very elderly; humans; human; male; female; article; obinutuzumab; polatuzumab vedotin; positron emission tomography-computed tomography; b cell chronic lymphocytic leukemia; chimeric antigen receptor t-cell immunotherapy; immune effector cell associated neurotoxicity syndrome; receptors, chimeric antigen; low grade b cell lymphoma |
| Journal Title: | Haematologica |
| Volume: | 109 |
| Issue: | 11 |
| ISSN: | 0390-6078 |
| Publisher: | Ferrata Storti Foundation |
| Date Published: | 2024-11-01 |
| Start Page: | 3566 |
| End Page: | 3577 |
| Language: | English |
| DOI: | 10.3324/haematol.2023.284664 |
| PUBMED: | 38899351 |
| PROVIDER: | scopus |
| PMCID: | PMC11532690 |
| DOI/URL: | |
| Notes: | Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PubMed and PDF -- Source: Scopus |
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