For patients with relapsed/refractory mantle cell lymphoma Lunsumio plus Polivy was associated with durable responses.
Among patients with relapsed/refractory mantle cell lymphoma (MCL) with prior exposure to BTK inhibition, treatment with Lunsumio (mosunetuzumab-axgb) plus Polivy (polatuzumab vedotin-piiq) was associated with durable responses and was found to be well tolerated, clinical trial results have shown.
Findings from an MCL dose-expansion cohort of a phase 2 trial were presented at the 2025 SOHO Annual Meeting.
Among all treated patients (42 patients), the overall response rate (ORR) was 88%; the complete response (CR) and partial response (PR) rates were 79% and 9%, respectively. The efficacy of this combination was observed across high-risk patient subgroups, including those at least 70 years of age (18 patients; ORR, 83%; CR rate, 78%; PR rate, 5%), those who had received prior CAR-T cell therapy (11 patients; 91%; 82%; 9%), those with a Ki-67 score of at least 50% (28 patients; 93%; 79%; 14%), those with pleomorphic or blastoid MCL (16 patients; 94%; 69%; 25%), and those with TP53 mutations or deletions (13 patients; 100%; 92%; 8%).
Overall response rate: patients who responded partially or completely to treatment.
Progression-free survival: the time a patient lives without their disease spreading or worsening.
Overall survival: the time a patient lives, regardless of disease status.
“[Lunsumio] and [Polivy], in my opinion, is going to be a good off-the-shelf option for relapsed/refractory MCL before or after CAR T-cell therapy,” lead study author Dr. Michael L. Wang, said in the presentation.
Wang is a professor in the Department of Lymphoma/Myeloma and the Department of Stem Cell Transplantation in the Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center in Houston.
Lunsumio is a CD20xCD3-directed, T-cell engaging bispecific antibody. Polivy is a CD79-directed antibody-drug conjugate.
“The two are complementary in their mechanisms of action,” Wang noted. “They were synergistic in preclinical studies.”
Previous findings from the dose-expansion large B-cell lymphoma (LBCL) cohort (98 patients) of the phase 2 study showed that at a median follow-up of 23.9 months, Lunsumio plus Polivy elicited an ORR of 59.2% and a CR rate of 45.9%. Furthermore, the median duration of CR was not reached.
This phase 2 study is investigating the efficacy, safety, pharmacokinetics and pharmacodynamics of Lunsumio plus Polivy in patients with B-cell non-Hodgkin lymphoma, including LBCL, follicular lymphoma and MCL.
Patients received the investigational combination in a fixed-duration treatment approach that included Lunsumio administered subcutaneously at 45 mg in 21-day cycles (5-mg step-up dosing occurred in cycle 1) for a total of 17 cycles; and intravenous Polivy administered at 1.8 mg/kg on day 1 of cycles 1 through 6. Hospitalization was not required. Patients received corticosteroid premedication before each dose in cycle 1.
Patients had a median age of 68 years and had received three prior lines of therapy. Prior therapies included BTK inhibition (100%), CAR T-cell therapy (26%) and autologous stem cell transplant (31%). In total, 93% of patients were refractory to their last prior therapy. TP53 mutations or deletions were present in 39% of patients, 38% of patients had blastoid or pleomorphic disease, and 43% of patients had bone marrow involvement. Ki-67 scores of at least 30% and at least 50% were reported in 76% and 67% of patients, respectively. Additionally, 48% of patients had a simplified International Prognostic Index for MCL score of at least 6. Overall, 71% of patients had at least three high-risk features.
“This is a high-risk, heavily treated population,” Wang contextualized.
The responses observed with this combination were early and durable, Wang noted. At a median follow-up of 15.9 months, among all responders (37 patients), the median time to first response was 2.7 months, the median DOR was not reached and the 12-month response rate was 66%. Among complete responders (33 patients), the median time to first CR was 2.8 months, the median duration of CR was not reached and the 12-month response rate was 71.9%.
Among all treated patients, the median progression-free survival (PFS) was 18.6 months, and the 12-month PFS rate was 74.8%. The median overall survival (OS) was 20.7 months and the 12-month OS rate was 83.1%.
All patients experienced side effects, and 93% of patients experienced treatment-related side effects. The rates of grade 3 (severe)/4 (life-threatening) side effects and treatment-related side effects were 69% and 60%, respectively. Serious side effects and treatment-related side effects were reported in 62% and 41% of patients, respectively. Grade 5 (fatal) side effects and treatment-related side effects occurred in 12% and 2% of patients, respectively; these included COVID-19 pneumonia (three patients), pneumonia (one patient) and West Nile virus encephalitis (one patient). Treatment discontinuation related to side effects and treatment-related side effects occurred in 24% and 12% of patients, respectively. Patients received a median of 15 Lunsumio cycles and six Polivy cycles.
Side effects and treatment-related side effects that occurred in at least 20% of patients included fatigue, injection site reaction, neutropenia/decreased neutrophil counts, diarrhea, cytokine release syndrome (CRS), nausea, dyspnea, constipation, cough, headache, pyrexia, thrombocytopenia/decreased platelet counts, COVID-19 and myalgia. Side effects of interest included injection site reaction (grade 1 (mild), 52%; grade 2 (moderate), 5%), peripheral neuropathy (grade 1, 29%; grade 2, 12%), immune effector cell–associated neurotoxicity syndrome (grade 2, 2%), infections (any grade, 71%; grade 3/4, 14%; grade 5, 12%), tumor flare (grade 1, 5%; grade 2, 7%), neutropenia/decreased neutrophil counts (any grade, 45%; grade 3/4, 41%), and febrile neutropenia (grade 3, 5%).
Notably, B-cell depletion occurred rapidly during treatment, and investigators observed recovery of B-cell counts following treatment.
