Abstract
Introduction Mosunetuzumab (mosun) is a CD20xCD3 bispecific antibody approved as a single agent for treatment of follicular lymphoma. It is also being studied in combination with other systemic therapies for aggressive B-cell lymphomas. Here, we present real-world outcomes of mosun use for both indolent and aggressive lymphomas.
Methods We performed a retrospective multicenter observational study of patients who received mosun for B-cell non-Hodgkin lymphoma between June 1, 2023 and May 15, 2025 at 9 centers comprising the Collaborative US Bispecific Consortium (CUBIC). Survival analysis was performed using the Kaplan-Meier method. Trial eligibility was determined by comparing laboratory and performance status data at time of mosun initiation to inclusion criteria of mosun trials in indolent (Budde et al. Lancet Onc. 2022) and aggressive (Budde et al. Nat. Med. 2024) lymphomas.
Results We identified 107 patients who received mosun as part of a standard-of-care regimen. 81 patients (76%) had indolent lymphomas (77 with follicular lymphoma, 4 with other subtypes) and 26 patients (24%) had aggressive lymphomas (15 with mantle cell lymphoma [MCL], 11 with diffuse large B-cell lymphoma [DLBCL]).
Indolent Lymphomas In the indolent cohort, median age was 68 years (range 33-92), 56% were male, 85% White and 7% Hispanic. Median prior lines of therapy was 3 (range 1-14). 14 patients (17%) had received prior CAR T cell therapy, 6 (7%) had prior autologous stem cell transplant, and 2 (3%) had prior allogeneic stem cell transplant. Of patients with data available to assess trial-eligibility, 73% were trial-eligible.
Mosun was given as a single agent in 79 patients (98%). 73 patients (90%) received their first full cycle of mosun as an outpatient. 29 patients (36%) developed cytokine release syndrome (CRS), of which maximum grade was 1 in 22 patients, 2 in 5 patients, 3 in 1 patient and not documented in 1 patient. One patient developed grade 1 immune effector cell-associated neurotoxicity syndrome (ICANS). 21 patients (26%) developed infections following treatment.
In the 75 evaluable patients from this cohort, best response was CR in 53 (71%), PR in 13 (17%), SD in 3 (4%) and PD in 6 (8%). With median follow-up 13.2 months, median PFS was 17.7 months (95% CI 13.5-21.9 months) and median OS was not reached. There was no difference in ORR, CRR, CRS rate, ICANS rate, PFS or OS between trial-eligible and ineligible patients.
Aggressive Lymphomas In the aggressive cohort, median age was 67 years (range 40-85), 65% were male, 81% White and 23% Hispanic. Median prior lines of therapy was 4 (range 1-8). 14 patients (54%) had received prior CAR T cell therapy and 4 (15%) had prior autologous stem cell transplant. Of patients with data available to assess trial eligibility, only 43% were trial-eligible.
All 15 patients with MCL were treated with mosun combined with polatuzumab vedotin (pola). 5 patients (33%) developed CRS, of which maximum grade was 1 in 3 patients and 2 in 2 patients. 3 patients (20%) developed infections after treatment. In the 12 evaluable patients, best response was CR in 8 (67%), PR in 3 (25%) and PD in 1 (8%). With median follow-up 6.1 months, median PFS and OS were not reached.
Of the 11 patients with DLBCL, 6 were treated with single-agent mosun and 5 with mosun/pola. 4 patients developed CRS, of which maximum grade was 1 in 2 patients and 2 in 2 patients. 2 patients (18%) developed infections after treatment. Best response was CR in 5 patients (45%), PR in 1 patient (9%), SD in 2 patients (18%), and PD in 3 patients (27%). 3 patients treated with single-agent mosun achieved CR. With median follow-up 12.7 months, median PFS was 2.1 months (95% CI 2.5-15.3 months) and median OS was not reached.
There was no significant difference in ORR, CRR, CRS rate, ICANS rate, PFS or OS between patients with MCL and DLBCL or between trial-eligible and ineligible patients.
Conclusions Mosun was well-tolerated and effective against a variety of lymphoma subtypes in a real-world setting. In indolent lymphomas, outcomes of single-agent mosun were comparable to those reported in the registrational trial, with a strikingly low rate of ICANS and high-grade CRS. Despite a heavily pre-treated and largely trial-ineligible population, high response rates were seen with mosun/pola in both MCL and DLBCL, with some complete responses noted with single-agent mosun in DLBCL. Longer follow-up is needed to determine response durability.
