Allogeneic hematopoietic cell transplantation after chimeric antigen receptor T cell therapy in large B cell lymphoma Journal Article
| Authors: | Fried, S.; Shouval, R.; Walji, M.; Flynn, J. R.; Yerushalmi, R.; Shem-Tov, N.; Danylesko, I.; Tomas, A. A.; Fein, J. A.; Devlin, S. M.; Sauter, C. S.; Shah, G. L.; Kedmi, M.; Jacoby, E.; Shargian, L.; Raanani, P.; Yeshurun, M.; Perales, M. A.; Nagler, A.; Avigdor, A.; Shimoni, A. |
| Article Title: | Allogeneic hematopoietic cell transplantation after chimeric antigen receptor T cell therapy in large B cell lymphoma |
| Abstract: | Anti-CD19 chimeric antigen receptor T cell (CAR-T) therapy has transformed the care of patients with relapsed/refractory large B cell lymphoma (LBCL). However, approximately 60% of CAR-T recipients ultimately will experience disease recurrence or progression. Salvage therapies after CAR-T treatment failures are of limited efficacy and have a short duration of response. The objective of the present study was to evaluate the role of allogeneic hematopoietic cell transplantation (allo-HCT) after CAR-T therapy in LBCL patients. This was a multicenter observational study reporting the outcome of 39 adult LBCL patients who underwent allo-HCT following anti-CD19 CAR-T therapy. The median patient age was 47 years (range, 20 to 68 years). HLA-matched sibling, HLA-matched unrelated, and alternative donors were used in 36%, 36%, and 28% of transplantations, respectively. Conditioning regimens were primarily of low or intermediate intensity. Disease status at allo-HCT was complete response in 41%, partial response in 38%, and progressive disease in 21%. Allo-HCT was performed at a median of 127 days (range, 82 to 206 days) after CAR-T therapy. A high incidence of hepatic toxicity (28%), including sinusoidal obstruction syndrome (15.4%; 95% confidence interval; [CI], 6.2% to 28.5%), was observed. The 1-year cumulative incidence of grade II-IV and grade III-IV acute graft-versus-host disease (GVHD) was 38.5% (95% CI, 23.2% to 53.6%) and 15.4% (95% CI, 6.1% to 28.5%), respectively. The 2-year cumulative incidence of moderate-severe chronic GVHD was 11.1% (95% CI, 3.3% to 24.3%). Overall, 2-year nonrelapse mortality and relapse/progression incidence were 26% (95% CI, 13% to 41%) and 43% (95% CI, 27% to 59%), respectively. With a median follow-up of 32 months, the 2-year overall survival (OS) and progression-free survival (PFS) were 45% (95% CI, 31% to 66%) and 31% (95% CI, 19% to 50%), respectively. In multivariable analyses, pre-HCT elevated lactate dehydrogenase level and transformed lymphoma were predictive of OS and PFS, respectively. Our data suggest that allo-HCT after anti-CD19 CAR-T treatment failure is feasible with a relatively promising efficacy but possibly high toxicity rate. © 2022 The American Society for Transplantation and Cellular Therapy |
| Keywords: | adult; cancer survival; clinical article; controlled study; aged; middle aged; young adult; overall survival; clinical trial; cancer recurrence; cancer radiotherapy; methotrexate; follow up; progression free survival; liver toxicity; phase 2 clinical trial; neoplasm recurrence, local; cohort analysis; cyclophosphamide; hematopoietic stem cell transplantation; retrospective study; alanine aminotransferase; aspartate aminotransferase; acute graft versus host disease; chronic graft versus host disease; hla matching; nonhodgkin lymphoma; karnofsky performance status; multicenter study; tumor recurrence; graft versus host reaction; recurrent disease; chimeric antigen receptor; allogeneic hematopoietic stem cell transplantation; therapy effect; lactate dehydrogenase; hyperbilirubinemia; clinical effectiveness; large cell lymphoma; lymphoma, large b-cell, diffuse; phase 1 clinical trial; observational study; toxicity; gvhd; calcineurin inhibitor; graft vs host disease; sirolimus; cd19 antigen; thymocyte antibody; cumulative incidence; allogeneic hematopoietic cell transplantation; adverse event; liver venoocclusive disease; complication; blood donor; systemic mycosis; sinusoidal obstruction syndrome; overall response rate; diffuse large b cell lymphoma; mycophenolate mofetil; humans; human; article; pembrolizumab; large b cell lymphoma; positron emission tomography-computed tomography; tisagenlecleucel t; chimeric antigen receptor t-cell immunotherapy; alanine aminotransferase level; aspartate aminotransferase level; axicabtagene ciloleucel; lisocabtagene maraleucel; haploidentical donor; matched sibling donor; receptors, chimeric antigen |
| Journal Title: | Transplantation and Cellular Therapy |
| Volume: | 29 |
| Issue: | 2 |
| ISSN: | 2666-6375 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2023-02-01 |
| Start Page: | 99 |
| End Page: | 107 |
| Language: | English |
| DOI: | 10.1016/j.jtct.2022.10.026 |
| PUBMED: | 36343892 |
| PROVIDER: | scopus |
| PMCID: | PMC10387120 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in PDF. Corresponding author is MSK author Roni Shouval -- Export Date: 1 March 2023 -- Source: Scopus |
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