For sufferers with relapsed/refractory mantle cell lymphoma Lunsumio plus Polivy was related to sturdy responses. Picture generated by Google Gemini.
Amongst sufferers with relapsed/refractory mantle cell lymphoma (MCL) with prior publicity to BTK inhibition, remedy with Lunsumio (mosunetuzumab-axgb) plus Polivy (polatuzumab vedotin-piiq) was related to sturdy responses and was discovered to be nicely tolerated, medical trial outcomes have proven.
Findings from an MCL dose-expansion cohort of a part 2 trial have been offered on the 2025 SOHO Annual Assembly.
Amongst all handled sufferers (42 sufferers), the general response fee (ORR) was 88%; the entire response (CR) and partial response (PR) charges have been 79% and 9%, respectively. The efficacy of this mix was noticed throughout high-risk affected person subgroups, together with these at the very least 70 years of age (18 sufferers; ORR, 83%; CR fee, 78%; PR fee, 5%), those that had acquired prior CAR-T cell remedy (11 sufferers; 91%; 82%; 9%), these with a Ki-67 rating of at the very least 50% (28 sufferers; 93%; 79%; 14%), these with pleomorphic or blastoid MCL (16 sufferers; 94%; 69%; 25%), and people with TP53 mutations or deletions (13 sufferers; 100%; 92%; 8%).
Glossary
Total response fee: sufferers who responded partially or fully to remedy.
Development-free survival: the time a affected person lives with out their illness spreading or worsening.
Total survival: the time a affected person lives, no matter illness standing.
“[Lunsumio] and [Polivy], for my part, goes to be a great off-the-shelf possibility for relapsed/refractory MCL earlier than or after CAR T-cell remedy,” lead examine creator Dr. Michael L. Wang, mentioned within the presentation.
Wang is a professor within the Division of Lymphoma/Myeloma and the Division of Stem Cell Transplantation within the Division of Most cancers Medication at The College of Texas MD Anderson Most cancers Middle in Houston.
What Was the Rationale for Investigating Lunsumio in Mixture With Polivy in Sufferers With MCL?
Lunsumio is a CD20xCD3-directed, T-cell partaking bispecific antibody. Polivy is a CD79-directed antibody-drug conjugate.
“The 2 are complementary of their mechanisms of motion,” Wang famous. “They have been synergistic in preclinical research.”
Earlier findings from the dose-expansion massive B-cell lymphoma (LBCL) cohort (98 sufferers) of the part 2 examine confirmed that at a median follow-up of 23.9 months, Lunsumio plus Polivy elicited an ORR of 59.2% and a CR fee of 45.9%. Moreover, the median length of CR was not reached.
What Was the Design of the MCL Portion of the Part 2 Research of Lunsumio Plus Polivy in Relapsed/Refractory MCL?
This part 2 examine is investigating the efficacy, security, pharmacokinetics and pharmacodynamics of Lunsumio plus Polivy in sufferers with B-cell non-Hodgkin lymphoma, together with LBCL, follicular lymphoma and MCL.
Sufferers acquired the investigational mixture in a fixed-duration remedy method that included Lunsumio administered subcutaneously at 45 mg in 21-day cycles (5-mg step-up dosing occurred in cycle 1) for a complete of 17 cycles; and intravenous Polivy administered at 1.8 mg/kg on day 1 of cycles 1 via 6. Hospitalization was not required. Sufferers acquired corticosteroid premedication earlier than every dose in cycle 1.
What Had been the Baseline Traits of Sufferers Included within the Trial?
Sufferers had a median age of 68 years and had acquired three prior strains of remedy. Prior therapies included BTK inhibition (100%), CAR T-cell remedy (26%) and autologous stem cell transplant (31%). In whole, 93% of sufferers have been refractory to their final prior remedy. TP53 mutations or deletions have been current in 39% of sufferers, 38% of sufferers had blastoid or pleomorphic illness, and 43% of sufferers had bone marrow involvement. Ki-67 scores of at the very least 30% and at the very least 50% have been reported in 76% and 67% of sufferers, respectively. Moreover, 48% of sufferers had a simplified Worldwide Prognostic Index for MCL rating of at the very least 6. Total, 71% of sufferers had at the very least three high-risk options.
“It is a high-risk, closely handled inhabitants,” Wang contextualized.
What Further Efficacy Information Had been Noticed With Lunsumio Plus Polivy?
The responses noticed with this mix have been early and sturdy, Wang famous. At a median follow-up of 15.9 months, amongst all responders (37 sufferers), the median time to first response was 2.7 months, the median DOR was not reached and the 12-month response fee was 66%. Amongst full responders (33 sufferers), the median time to first CR was 2.8 months, the median length of CR was not reached and the 12-month response fee was 71.9%.
Amongst all handled sufferers, the median progression-free survival (PFS) was 18.6 months, and the 12-month PFS fee was 74.8%. The median total survival (OS) was 20.7 months and the 12-month OS fee was 83.1%.
What Was the Security Profile of Lunsumio Plus Polivy in Sufferers With MCL?
All sufferers skilled unintended effects, and 93% of sufferers skilled treatment-related unintended effects. The charges of grade 3 (extreme)/4 (life-threatening) unintended effects and treatment-related unintended effects have been 69% and 60%, respectively. Critical unintended effects and treatment-related unintended effects have been reported in 62% and 41% of sufferers, respectively. Grade 5 (deadly) unintended effects and treatment-related unintended effects occurred in 12% and a couple of% of sufferers, respectively; these included COVID-19 pneumonia (three sufferers), pneumonia (one affected person) and West Nile virus encephalitis (one affected person). Therapy discontinuation associated to unintended effects and treatment-related unintended effects occurred in 24% and 12% of sufferers, respectively. Sufferers acquired a median of 15 Lunsumio cycles and 6 Polivy cycles.
Uncomfortable side effects and treatment-related unintended effects that occurred in at the very least 20% of sufferers included fatigue, injection website response, neutropenia/decreased neutrophil counts, diarrhea, cytokine launch syndrome (CRS), nausea, dyspnea, constipation, cough, headache, pyrexia, thrombocytopenia/decreased platelet counts, COVID-19 and myalgia. Uncomfortable side effects of curiosity included injection website response (grade 1 (delicate), 52%; grade 2 (reasonable), 5%), peripheral neuropathy (grade 1, 29%; grade 2, 12%), immune effector cell–related 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 quickly throughout remedy, and investigators noticed restoration of B-cell counts following remedy.
References
- Wang ML, Kamdar M, Assouline S, et al. Fastened-duration outpatient subcutaneous mosunetuzumab + polatuzumab vedotin reveals sturdy efficacy in a part II examine of relapsed/refractory post-BTKi mantle cell lymphoma. Introduced at: 2025 SOHO Annual Assembly. September 3-6, 2025; Houston, TX. Summary MCL-1493.
- Budde LE, Olszewski AJ, Assouline S, et al. Mosunetuzumab with polatuzumab vedotin in relapsed or refractory aggressive massive B cell lymphoma: a part 1b/2 trial. Nat Med. 2024;30(1):229-239. doi:10.1038/s41591-023-02726-5
- A examine to judge the security and efficacy of mosunetuzumab (BTCT4465A) together with polatuzumab vedotin in B-cell non-Hodgkin lymphoma. ClinicalTrials.gov. Up to date November 29, 2024. Accessed September 6, 2025. https://www.clinicaltrials.gov/examine/NCT03671018
