Abstract
Introduction
Chimeric antigen receptor (CAR)-T cells obtained long-term durability in about 30% to 40% of relapsed/refractory (r/r) B-cell non-Hodgkin lymphoma (B-NHL). Maintenance therapy after CAR-T is necessary, and PD1 inhibitor is one of the important maintenance therapy options.
Methods
A total of 173 r/r B-NHL patients treated with PD1 inhibitor maintenance following CD19/22 CAR-T therapy alone or combined with autologous hematopoietic stem cell transplantation (ASCT) from March 2019 to July 2022 were assessed for eligibility for two trials. There were 81 patients on PD1 inhibitor maintenance therapy.
Results
In the CD19/22 CAR-T therapy trial, the PD1 inhibitor maintenance group indicated superior objective response rate (ORR) (82.9% vs 60%; P = 0.04) and 2-year progression-free survival (PFS) (59.8% vs 21.3%; P = 0.001) than the non-maintenance group. The estimated 2-year overall survival (OS) was comparable in the two groups (60.1% vs 45.1%; P = 0.112). No difference was observed in the peak expansion levels of CD19 CAR-T and CD22 CAR-T between the two groups. The persistence time of CD19 and CD22 CAR-T in the PD1 inhibitor maintenance group was longer than that in the non-maintenance group. In the CD19/22 CAR-T therapy combined with ASCT trial, no significant differences in ORR (81.4% vs 84.8%; P = 0.67), 2-year PFS (72.3% vs 74.9%; P = 0.73), and 2-year OS (84.1% vs 80.7%; P = 0.79) were observed between non-maintenance and PD1 inhibitor maintenance therapy groups. The peak expansion levels and duration of CD19 and CD22 CAR-T were not statistically different between the two groups. During maintenance treatment with PD1 inhibitor, all adverse events were manageable. In the multivariable analyses, type and R3m were independent predictive factors influencing the OS of r/r B-NHL with PD1 inhibitor maintenance after CAR-T therapy.
Conclusion
PD1 inhibitor maintenance following CD19/22 CAR-T therapy obtained superior response and survival in r/r B-NHL, but not in the trial of CD19/22 CAR-T cell therapy combined with ASCT.
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Data availability
The data supporting the current study will be made available by the authors, without reservation.
Abbreviations
- CAR-T:
-
Chimeric antigen receptor T-cell
- r/r:
-
Relapsed or refractory
- B-NHL:
-
B-cell non-Hodgkin-lymphoma
- PD1:
-
Programmed cell death protein 1
- ASCT:
-
Autologous hematopoietic stem cell transplantation
- ORR:
-
Objective response rate
- PFS:
-
Progression-free survival
- OS:
-
Overall survival
- DLBCL:
-
Diffuse large B-cell lymphoma
- PMBCL:
-
Primary mediastinal large B-cell lymphoma
- FL:
-
Follicular lymphoma
- PDL1:
-
Programmed cell death 1 ligand 1
- PBMC:
-
Peripheral blood mononuclear cell
- CT:
-
Computed tomography
- CRS:
-
Cytokine release syndrome
- ICANS:
-
Immune effector cell-associated neurotoxicity syndrome
- OR:
-
Objective response
- CR:
-
Complete remission
- PR:
-
Partial remission
- SD/PD:
-
Stable disease/progressive disease
- DOR:
-
Duration of response
- IPI:
-
International prognostic index
- R3m:
-
OR at month 3
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Acknowledgements
The authors would like to thank all the patients who participated in this study and their families, Wuhan Biotechnology Co., Ltd. and our colleagues for their support.
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This work was supported by grants from the National High Technology Research and Development Program of China (Grant 2021YFA1101504).
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YZ and LJ conceived and designed the study. XZ revised the manuscript for submission. XZ, YY, NW, JW, JX, JW, LH, MZ, CL, YX, FM, YC, LJ, and YZ enrolled patients and provided patient care; XX collected and analyzed data and wrote the manuscript. All authors contributed to the article and approved the submitted version.
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Xin, X., Zhu, X., Yang, Y. et al. Efficacy of programmed cell death 1 inhibitor maintenance after chimeric antigen receptor T cells in patients with relapsed/refractory B-cell non-Hodgkin-lymphoma. Cell Oncol. (2024). https://doi.org/10.1007/s13402-024-00940-y
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DOI: https://doi.org/10.1007/s13402-024-00940-y