Effect of Timing of Bispecific Antibody Treatment for Patients With B-Cell Lymphomas Relapsing After CAR-T

The timing of bispecific antibody treatment administration following chimeric antigen receptor (CAR) T-cell therapy relapse may be associated with quality of response among patients with B-cell lymphomas, according to study results published in Blood Advances.

Specifically, investigators noted higher response to bispecific antibody treatment mosunetuzumab following CAR T-cell therapy was associated with increased time before mosunetuzumab administration for patients with B-cell lymphomas.

Mosunetuzumab has been approved for the treatment of B-cell lymphomas following CAR-T failure, however, research is limited on the optimal timing of mosunetuzumab administration and predictive biomarkers of response. Researchers evaluated data from phase1/2 trials of mosunetuzumab for clinical and immunological factors associated with therapeutic responses among patients with B-cell lymphomas previously treated with CAR-T therapy.

Among 30 patients, 90% were diagnosed with large B-cell lymphoma (LBCL), and 10% were diagnosed with follicular lymphoma (FL). Complete response was achieved by 23% of patients, and 17% had a partial response. Progression-free survival (PFS) was higher for patients who responded to mosunetuzumab (6.1 months), compared with patients who did not respond (1.2 months).  The median time from CAR-T to mosunetuzumab was 161 days (range, 35 to 1071), of which 40% was within 100 days, 43% within 101 and 365 days, and 17% more than 1 year after CAR-T therapy. Overall, all but 1 patient who were treated >9.5 months after CAR-T therapy had a response to mosunetuzumab.

Additionally, patients who responded had significantly higher lymphocyte counts (995 vs 400 cells/μL; P = .02) and greater increases in CD4 and CD8 T-cell counts (median change, 73 vs –90 cells/μL [P = .005] and 243 vs –103 cells/μL [P = .004], respectively), compared with patients who did not respond.  Additionally, patients who responded demonstrated an increase in activated CD8 cells (median fold change, 1.7; P = .02), while patients without a response exhibited a relative decrease in CAR transgene levels (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 [bispecific antibodies] after CAR-T,” they concluded. “These findings suggest an interaction between prior CAR-T and [bispecific antibody] outcomes and have implications for optimal timing of [bispecific antibodies after CAR-T.”

“Further investigations, including studies of alternative [bispecific antibodies], are needed to understand the mechanisms and generality of our observations,” the researchers added.

Source:

Chong EA, Penuel E, Napier EB, et al. Impact of prior CAR T-cell therapy on mosunetuzumab efficacy in patients with relapsed or refractory B-cell lymphomas. Blood Advances. Published online February 12, 2025. doi: 10.1182/bloodadvances.2024013640