Allogeneic Hematopoietic Cell Transplantation after Chimeric Antigen Receptor T Cell Therapy in Large B Cell Lymphoma

Shalev Fried, Roni Shouval*, Moneeza Walji, Jessica R. Flynn, Ronit Yerushalmi, Noga Shem-Tov, Ivetta Danylesko, Ana Alarcon Tomas, Joshua A. Fein, Sean M. Devlin, Craig S. Sauter, Gunjan L. Shah, Meirav Kedmi, Elad Jacoby, Liat Shargian, Pia Raanani, Moshe Yeshurun, Miguel Angel Perales, Arnon Nagler, Abraham AvigdorAvichai Shimoni

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)99-107
Number of pages9
JournalTransplantation and Cellular Therapy
Volume29
Issue number2
DOIs
StatePublished - Feb 2023

Keywords

  • Allogeneic hematopoietic cell transplantation
  • Chimeric antigen receptor
  • GVHD
  • Large B cell lymphoma
  • Sinusoidal obstruction syndrome
  • Toxicity

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