Published on November 09, 2023
Mosunetuzumab with polatuzumab vedotin in relapsed or refractory aggressive large B cell lymphoma: a phase 1b/2 trial
by Alex Kadhim
Analysis from a phase 1b/2 trial evaluating the safety and efficacy of mosunetuzumab (BTCT4465A; a CD20xCD3 T-cell-engaging bispecific antibody) plus polatuzumab vedotin (an anti-CD79B antibody-drug conjugate), recently published in Nature Medicine, has found that this combination (mosun-pola) was effective and safe as a second-line therapy for relapsed or refractory large B cell lymphoma (R/R LBCL). Overall, mosun-pola was able to elicit durable responses in these patients, suggesting it holds promise as a treatment for transplant-ineligible R/R LCBL. This collaborative effort spanned multiple cancer research centers and was spearheaded by Hoffmann-La Roche.
The most common aggressive non-Hodgkin lymphoma (NHL) is LBCL, with patients currently being treated with rituximab-based immunochemotherapy. Unfortunately, a significant proportion of patients either do not respond or experience relapse. Second-line treatments including salvage chemotherapy followed by stem cell transplant or CAR-T cell therapy, are options, but better treatments are needed. Both mosunetuzumab and polatuzumab vedotin have shown promise individually in R/R NHL. In combination, mosun-pola targets distinct aspects of malignant B cell biology, and preliminary evidence suggests a favorable safety profile. This study sought to report the primary analysis of the ongoing phase 1b/2 mosun-pola trial (NCT03671018).
In total, 120 patients (22 in the dose-escalation phase and 98 in the dose-expansion phase) with R/R NHL were examined. The primary endpoint was the overall response rate (ORR) assessed by the independent review committee (IRC). Secondary endpoints included investigator-assessed ORR, complete response rates (CRR), duration of response, progression-free survival (PFS), and overall survival (OS). During dose expansion, the ORR by IRC and CRRs were 59.2% (58/98; 95% CI: 48.8–69.0) and 45.9% (45/98; 95% CI: 35.8–56.3), respectively, with a median follow-up of 23.9 months. Median PFS was 11.4 months (95% CI: 6.2–18.7), and median OS was 23.3 months (95% CI: 14.8–not estimable). Common grade 3 or higher adverse events included neutropenia (25.0%, 30/120) and fatigue (6.7%, 8-120), while any-grade cytokine release syndrome occurred in 16.7% of patients. These results suggest promising efficacy and an acceptable safety profile for the mosun-pola combination therapy.
Reference:
Budde LE, Olszewski AJ, Assouline S, et al. Mosunetuzumab with polatuzumab vedotin in relapsed or refractory aggressive large B cell lymphoma: a phase 1b/2 trial. Nat Med. Published online December 10, 2023.
https://doi.org/10.1038/s41591-023-02726-5
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