A retrospective comparison of allogenic and autologous chimeric antigen receptor T cell therapy targeting CD19 in patients with relapsed/refractory acute lymphoblastic leukemia

Bone Marrow Transplant. 2019 Aug;54(8):1208-1217. doi: 10.1038/s41409-018-0403-2. Epub 2018 Dec 5.

Abstract

The source of CAR T cells can be autologous (autoCAR) or allogeneic (alloCAR). The latter is seen in patients with a history of allogeneic hematopoietic stem cell transplantation, and can be either donor-derived (DD-alloCAR) or recipient-derived (RD-alloCAR). While autoCAR is activated by CAR only, alloCAR receives activation signals from both T-cell receptor (TCR) and CAR. As a result, the biological differences could impact clinical outcomes. We retrospectively reviewed 31 patients: 17 received autoCAR, 11 received RD-alloCAR, and 3 received DD-alloCAR. After a median follow-up of 9 months, CR rate was 88.2% (95% CI 63.6-98.5%) in autoCAR and 100% (95% CI 71.5-100%) in RD-alloCAR. The median peak expansion in the autoCAR was significantly higher than the RD-alloCAR group (p = 0.007). RD-alloCAR group had significantly less patients with severe CRS (Grade ≥ 3) than the autoCAR group (p = 0.049). Acute graft-versus-host disease (GVHD) occurred in 2 (18.2%) of RD-alloCAR patients and 1 (33.3%) of DD-alloCAR patients. Univariate subgroup analysis of alloCAR group showed the presence of cGVHD at the time of T-cell collection was significantly associated with less than 6-month relapses (p = 0.022). RD-alloCAR patients with or without cGVHD at PBMC collection did not differ regarding the peak CAR T-cell expansion, CRS grades and OS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD19 / immunology*
  • Female
  • Hematopoietic Stem Cell Transplantation / methods*
  • Humans
  • Male
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology
  • Receptors, Chimeric Antigen / metabolism*
  • Recurrence
  • Retrospective Studies
  • T-Lymphocytes / immunology*
  • Transplantation Conditioning / methods*
  • Transplantation, Homologous / methods*

Substances

  • Antigens, CD19
  • Receptors, Chimeric Antigen