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

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.

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Acknowledgements

We thank Qu Cui, PhD for the editorial assistance.

Funding

This work was supported by the grants from 973 Program (2015CB964900), the Natural Science Foundation of China (81470341, 81770201, 81730008), Key Project of Science and Technology Department of Zhejiang Province (2018C03016-2, 2015C03G2150011), Zhejiang public welfare foundation (GF18H180002).

Author contributions

H.H. designed the study. Y.H. and J.W. were responsible for writing the manuscript. J.W. and J.Y. collected and analyzed all data. G.W., Y.L., J.S., W.W., K.Z., L.X., Y.Z., Z.W., H.X., and A.H.C. participated in the study. All authors approved the final version of the manuscript.

Author information

Correspondence to He Huang.

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Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This study was conducted according to the ethical principles for medical research involving human subjects as stated in the Declaration of Helsinki. The study protocol was reviewed and approved by the Institutional Review Boards of the First Affiliated Hospital, School of Medicine, Zhejiang University. All participants signed informed consent.

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