Primary phase 2 efficacy and safety results of M-Pola in relapsed/refractory LBCL

Encouraging efficacy data were reported from a phase 1b/2 study for the combination of mosunetuzumab plus polatuzumab vedotin (M-Pola) in participants with relapsed/refractory (R/R) large B-cell lymphoma (LBCL). A phase 3 study testing this combination regimen has been initiated based on the findings of the current study.

Mosunetuzumab is a CD20 and CD3 T-cell engaging bispecific antibody, redirecting T cells to eliminate B-cells, and polatuzumab vedotin targets CD79b to deliver a microtubule-disrupting agent, directly eliminating B cells. “Thus, these agents target B lymphoma cells via different mechanisms of action,” introduced Dr Elizabeth Budde (City of Hope National Medical Center, CA, USA).

Dr Budde presented the primary findings of the phase 1b/2 study (NCT03671018) evaluating a regimen of M-Pola in 98 participants with R/R LBCL (including diffuse LBCL not otherwise specified, high-grade B-cell lymphoma, transformed follicular lymphoma, and follicular lymphoma grade 3b) [1]. The primary endpoint was the best overall response rate (ORR) assessed by an independent review committee using the Lugano 2014 criteria [2].

After 23.9 months of follow-up, the best ORR was 59.2% in the trial participants compared with 42.0% in a cohort of historical controls, derived from the ROMULUS study (P=0.0003). The complete response rate was 45.9%. The median duration of response was 20.8 months and the median duration of complete response was not reached at the time of analysis. The median progression-free survival and median overall survival were 11.4 months and 23.3 months, respectively. “Importantly, we saw durable responses in participants who had received previous CAR T-cell therapy, with the best ORR of 57.1% and a median duration of response that was not reached,” specified Dr Budde.

The safety profile of the combination regimen was manageable, with grade 3–4 treatment-related adverse events (AEs) occurring in 34.7% of the participants. The most common AEs were fatigue, decreased neutrophil counts, and nausea. Finally, cytokine release syndrome (CRS) was reported in 18.4% of the participants (n=18), with 3 cases presenting with grade 3. “The cases of CRS were confined to cycle 1 of treatment,” stressed Dr Budde. Any-grade ICANS occurred in 5.1% of the participants, grade 1–2 peripheral neuropathy was reported in 28.5%, grade 3–4 neutropenia in 20.4%, and serious infections of grade 3–4 in 9.1% of the subjects. Finally, the median time-to-B-cell recovery was 12.4 months after completion of therapy.

“M-Pola is a promising therapy with a manageable safety profile for patients with R/R LBCL,” concluded Dr Budde. Based on the findings of the current study, a phase 3 study testing this combination regimen has been initiated (NCT05171647).

1. Budde LE, et al. Mosunetuzumab plus polatuzumab vedotin demonstrates a favorable safety profile and efficacy in patients with relapsed/refractory LBCL: primary analysis of a phase Ib/II study. Abstract 613, 65^th ASH Annual Meeting, 9–12 December 2023, San Diego, CA, USA.
2. Cheson BC et al. J Clin Oncol. 2014;32(27):3059-3068.

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Posted on 7 February 202422 February 2024