Mosun-Pola in R/R MCL after BTKi therapy: A phase Ib/II study

Results from the phase II dose-expansion cohort of an open-label, multicenter phase Ib/II study (NCT03671018), evaluating mosunetuzumab + polatuzumab vedotin (Mosun-Pola) in adults with relapsed/refractory (R/R) mantle cell lymphoma (MCL) after prior Bruton’s tyrosine kinase inhibitor (BTKi) therapy, were published in Blood by Budde et al. The study enrolled 42 patients with R/R MCL after ≥2 prior lines of therapy (LoT), including an anti-CD20 therapy, a BTKi, and an anthracycline or bendamustine. Patients received fixed-duration subcutaneous mosunetuzumab for 17 cycles plus intravenous polatuzumab vedotin for 6 cycles. The primary endpoint was independent review committee (IRC)-assessed best objective response rate (ORR).

Key data: At 15.9 months’ median follow-up, the IRC-assessed ORR was 88.1% (95% confidence interval [CI], 74.4–96.0; p < 0.0001 vs historical control of 30%), with a complete response (CR) rate of 78.6% (95% CI, 63.2–89.7). Median time to first response was 2.7 months, mostly corresponding to the first response assessment. Median duration of response (DoR) and duration of CR (DoCR) were not reached. Median progression-free survival (PFS) was 18.6 months (95% CI, 13.9–not estimable [NE]), while median overall survival (OS) was 20.7 months (95% CI, 17.0–NE). Efficacy was consistent across high-risk subgroups, including those who relapsed after chimeric antigen receptor (CAR) T-cell therapy and those with known TP53-aberrant disease. Grade 3/4 adverse events (AEs) occurred in 69.0% of patients, most commonly neutropenia (40.5%), anemia (9.5%), and pneumonia (9.5%). Cytokine release syndrome (CRS) occurred in 42.9% of patients (all Grade 1–2).

Key learning: Fixed-duration Mosun-Pola demonstrated high CR rates with a manageable safety profile in patients with R/R MCL, including patients with high-risk biological features and/or who relapsed post-CAR T-cell therapy, supporting further evaluation of this combination and its optimal sequencing with newer therapies.