Impact of prior CAR T-cell therapy on mosunetuzumab efficacy in patients with relapsed or refractory B-cell lymphomas

Mosunetuzumab and other CD20/CD3 bispecific antibodies (BsAbs) have efficacy in B-cell lymphomas relapsing after or refractory to CD19-directed chimeric antigen receptor (CAR)-modified T cells (CAR-T). The optimal timing of BsAbs and biomarkers of BsAb response after CAR-T are unknown. We addressed these questions using clinical data and blood samples from patients previously treated with CAR-T and subsequently treated on a phase 1/2 study of mosunetuzumab. Thirty patients had paired samples at baseline and after 1 cycle of mosunetuzumab. The median time from CAR-T to mosunetuzumab was significantly longer for responding than for nonresponding patients (P = .006, unadjusted for multiple comparisons). Most patients (20/30) did not receive intervening therapy between CAR-T administration and mosunetuzumab. The remainder of patients received 1 intervening therapy after a protocol-mandated drug washout. After mosunetuzumab, responding patients had higher lymphocytes (995 vs 400 cells per μL; P = .02) and greater increases in CD4 and CD8 cells (median change, 73 vs -90 cells per μL [P = .005] and 243 vs -103 cells per μL [P = .004], respectively). Additionally, responding patients had an increase in activated CD8 cells (median fold change, 1.7; P = .02). Nonresponders had a relative decrease in CAR transgene levels (n = 16; P = .04). This is, to our knowledge, the first study to assess changes in lymphocytes, T cells, and CAR transgene levels in patients treated with BsAbs after CAR-T. These findings suggest an interaction between prior CAR-T and BsAb outcomes and have implications for optimal timing of BsAb after CAR-T. The trial was registered at www.ClinicalTrials.gov as #NCT02500407.

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Publication Details

Journal
Blood Advances
Published
2024-11-21
DOI
https://doi.org/10.1182/bloodadvances.2024013640
Citations
10
Primary Topic
CAR-T cell therapy research
Type
article
Field-Weighted Citation Impact
2.83

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article

Impact of prior CAR T-cell therapy on mosunetuzumab efficacy in patients with relapsed or refractory B-cell lymphomas

Ian W. Flinn, Elise A. Chong, Joseph A. Fraietta, Loretta J. Nastoupil et al.
10 citations
Blood Advances
CAR-T cell therapy research
2.83
article

Impact of prior CAR T-cell therapy on mosunetuzumab efficacy in patients with relapsed or refractory B-cell lymphomas

Ian W. Flinn, Elise A. Chong, Joseph A. Fraietta, Loretta J. Nastoupil, Emeline R. Chong, Keith Fay, Shen Yin, Matthew J. Matasar, Mazyar Shadman, Francesc Bosch, Ellen Napier, Michael C. Wei, Nancy L. Bartlett, Stephen J. Schuster, Lihua E. Budde, Anita Kumar, André Goy, Elicia Penuel, Rachel K Lundberg, Mei Wu
article en
10 citations

Abstract

Mosunetuzumab and other CD20/CD3 bispecific antibodies (BsAbs) have efficacy in B-cell lymphomas relapsing after or refractory to CD19-directed chimeric antigen receptor (CAR)-modified T cells (CAR-T). The optimal timing of BsAbs and biomarkers of BsAb response after CAR-T are unknown. We addressed these questions using clinical data and blood samples from patients previously treated with CAR-T and subsequently treated on a phase 1/2 study of mosunetuzumab. Thirty patients had paired samples at baseline and after 1 cycle of mosunetuzumab. The median time from CAR-T to mosunetuzumab was significantly longer for responding than for nonresponding patients (P = .006, unadjusted for multiple comparisons). Most patients (20/30) did not receive intervening therapy between CAR-T administration and mosunetuzumab. The remainder of patients received 1 intervening therapy after a protocol-mandated drug washout. After mosunetuzumab, responding patients had higher lymphocytes (995 vs 400 cells per μL; P = .02) and greater increases in CD4 and CD8 cells (median change, 73 vs -90 cells per μL [P = .005] and 243 vs -103 cells per μL [P = .004], respectively). Additionally, responding patients had an increase in activated CD8 cells (median fold change, 1.7; P = .02). Nonresponders had a relative decrease in CAR transgene levels (n = 16; P = .04). This is, to our knowledge, the first study to assess changes in lymphocytes, T cells, and CAR transgene levels in patients treated with BsAbs after CAR-T. These findings suggest an interaction between prior CAR-T and BsAb outcomes and have implications for optimal timing of BsAb after CAR-T. The trial was registered at www.ClinicalTrials.gov as #NCT02500407.

Blood AdvancesVol. 9(4)
Rutgers, The State University of New Jersey (US), City Of Hope National Medical Center (US), Hackensack University Medical Center (US), Memorial Sloan Kettering Cancer Center (US), The University of Texas MD Anderson Cancer Center (US), Washington University in St. Louis (US), Royal North Shore Hospital (AU), St Vincent's Hospital Melbourne (AU), Fred Hutch Cancer Center (US), Parker Institute for Cancer Immunotherapy (US), Center for Cancer and Blood Disorders (US), Vall d'Hebron Hospital Universitari (ES), UPMC Hillman Cancer Center (US), Tennessee Oncology (US), Hackensack Meridian Health (US), Vall d'Hebron Institute of Oncology (ES), Rutgers Cancer Institute (US), University of Pennsylvania (US)
Genentech
Good health and well-being
Openalex Percentile: Top 7%
CAR-T cell therapy research
2.83
DOIOpen Access PDFOpenAlex
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