Impact of prior CAR T-cell therapy on mosunetuzumab efficacy in patients with relapsed or refractory B-cell lymphomas
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...
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Elsevier
2025-02-01
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| Series: | Blood Advances |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2473952924006724 |
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| author | Elise A. Chong Elicia Penuel Ellen B. Napier Rachel K. Lundberg Lihua E. Budde Mazyar Shadman Matthew J. Matasar Nancy L. Bartlett Ian W. Flinn Francesc Bosch Keith Fay Andre Goy Anita Kumar Loretta J. Nastoupil Michael C. Wei Mei Wu Shen Yin Joseph A. Fraietta Emeline R. Chong Stephen J. Schuster |
| author_facet | Elise A. Chong Elicia Penuel Ellen B. Napier Rachel K. Lundberg Lihua E. Budde Mazyar Shadman Matthew J. Matasar Nancy L. Bartlett Ian W. Flinn Francesc Bosch Keith Fay Andre Goy Anita Kumar Loretta J. Nastoupil Michael C. Wei Mei Wu Shen Yin Joseph A. Fraietta Emeline R. Chong Stephen J. Schuster |
| author_sort | Elise A. Chong |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-ccaea24960464786b8012cda2e6aebdb |
| institution | Kabale University |
| issn | 2473-9529 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Blood Advances |
| spelling | doaj-art-ccaea24960464786b8012cda2e6aebdb2025-02-12T05:31:37ZengElsevierBlood Advances2473-95292025-02-0194696703Impact of prior CAR T-cell therapy on mosunetuzumab efficacy in patients with relapsed or refractory B-cell lymphomasElise A. Chong0Elicia Penuel1Ellen B. Napier2Rachel K. Lundberg3Lihua E. Budde4Mazyar Shadman5Matthew J. Matasar6Nancy L. Bartlett7Ian W. Flinn8Francesc Bosch9Keith Fay10Andre Goy11Anita Kumar12Loretta J. Nastoupil13Michael C. Wei14Mei Wu15Shen Yin16Joseph A. Fraietta17Emeline R. Chong18Stephen J. Schuster19Lymphoma Program, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PAGenentech, Inc, South San Francisco, CALymphoma Program, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PALymphoma Program, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PADepartment of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CAClinical Research Division, Fred Hutchinson Cancer Center and Hematology and Medical Oncology Division, University of Washington, Seattle WADivision of Blood Disorders, Rutgers Cancer Institute, New Brunswick, NJSiteman Cancer Center, Washington University School of Medicine, St. Louis, MOClinical Research, Tennessee Oncology and OneOncology, Nashville, TNDepartment of Hematology, Vall d’Hebron Institute of Oncology, Hospital Universitari Vall d’Hebron, Barcelona, SpainSt. Vincent’s Hospital and Royal North Shore Hospital, Sydney, AustraliaLymphoma Division, John Theurer Cancer Center, Hackensack Meridian Health, Hackensack, NJLymphoma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NYDepartment of Lymphoma and Myeloma, Division of Cancer Medicine, MD Anderson Cancer Center, Houston, TXGenentech, Inc, South San Francisco, CAGenentech, Inc, South San Francisco, CAGenentech, Inc, South San Francisco, CACenter for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA; Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PALymphoma Program, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PALymphoma Program, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA; Correspondence: Stephen J. Schuster, Lymphoma Program, Abramson Cancer Center, University of Pennsylvania, 3400 Civic Center Blvd, Philadelphia, PA 19104;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.http://www.sciencedirect.com/science/article/pii/S2473952924006724 |
| spellingShingle | Elise A. Chong Elicia Penuel Ellen B. Napier Rachel K. Lundberg Lihua E. Budde Mazyar Shadman Matthew J. Matasar Nancy L. Bartlett Ian W. Flinn Francesc Bosch Keith Fay Andre Goy Anita Kumar Loretta J. Nastoupil Michael C. Wei Mei Wu Shen Yin Joseph A. Fraietta Emeline R. Chong Stephen J. Schuster Impact of prior CAR T-cell therapy on mosunetuzumab efficacy in patients with relapsed or refractory B-cell lymphomas Blood Advances |
| title | Impact of prior CAR T-cell therapy on mosunetuzumab efficacy in patients with relapsed or refractory B-cell lymphomas |
| title_full | Impact of prior CAR T-cell therapy on mosunetuzumab efficacy in patients with relapsed or refractory B-cell lymphomas |
| title_fullStr | Impact of prior CAR T-cell therapy on mosunetuzumab efficacy in patients with relapsed or refractory B-cell lymphomas |
| title_full_unstemmed | Impact of prior CAR T-cell therapy on mosunetuzumab efficacy in patients with relapsed or refractory B-cell lymphomas |
| title_short | Impact of prior CAR T-cell therapy on mosunetuzumab efficacy in patients with relapsed or refractory B-cell lymphomas |
| title_sort | impact of prior car t cell therapy on mosunetuzumab efficacy in patients with relapsed or refractory b cell lymphomas |
| url | http://www.sciencedirect.com/science/article/pii/S2473952924006724 |
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