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Pembrolizumab May Reinvigorate T-Cells in CAR-T Patients Who Relapse
Pembrolizumab may reverse T-cell exhaustion in B-cell lymphoma patients who relapse after or become refractory to treatment with CD19-targeted CAR T-cells, according to a study conducted by mass cytometry and quantitative polymerase chain reaction (Q-PCR).
“CD19-directed chimeric antigen receptor–modified (CAR) T-cells achieve durable remissions in about 30% to 40% of relapsed/refractory large B-cell lymphomas…Patients who respond to pembrolizumab have CAR T-cells and non–CAR T-cells that are less exhausted compared with nonresponding patients,” wrote lead author Elise Chong, MD, Abramson Cancer Center, Philadelphia, and coauthors.
Researchers treated 12 patients with B-cell lymphomas, 9 of whom were refractory to CD19-directed CAR T-cell (4-1BB costimulated) therapy, and 3 of whom were relapsed. The relapsed/refractory patients received pembrolizumab 200 mg IV every 3 weeks. Median time from CAR T-cell infusion to first pembrolizumab dose was 3.3 months (range, 0.4-42.8 months).
Of the 12, 4 patients enjoyed clinical benefit: 1 had a complete response, while 2 had partial responses, and another had stable disease. The scientists performed mass cytometry by time of flight (CyTOF) on the 4 patients, and found an increase in the percentage of CAR T-cells. The researchers also performed Q-PCR, and determined that 3 of the 4 had increases in CAR19 transgene levels. Deep immune profiling using CyTOF revealed increased CAR T-cell activation and proliferation and less T-cell exhaustion in these subjects.
Neutropenia, the only grade ≥3 adverse event related to pembrolizumab, affected 3 of the 12 participants.
Source:
Chong E, Alanio C, Svoboda J, et al. Pembrolizumab for B-cell lymphomas relapsing after or refractory to CD19-directed CAR T-cell therapy. Blood. 2022 Feb 17;139(7):1026-1038.
