Mosunetuzumab Induces Response in Heavily Pre-Treated Patients With NHL

By Kerri Fitzgerald - Last Updated: December 12, 2019

The fully humanized immunoglobulin G1 bispecific CD3- and CD20-targeted antigen mosunetuzumab showed favorable tolerability and durable efficacy in heavily pre-treated patients with B-cell non-Hodgkin lymphoma (NHL), including those who progressed after receiving CAR T-cell therapy, according to data presented at the 2019 ASH Annual Meeting.

The ongoing open-label, multicenter, phase I/Ib, dose-escalation and -expansion GO29781 study assessed mosunetuzumab in patients with relapsed/refractory B-cell NHL. In group B from the study (n=218 as of June 4, 2019), patients received mosunetuzumab in step-up dosing on days one, eight, and 15 of cycle one and as a fixed dose on day one of each subsequent 21-day cycle, for a maximum of 17 cycles.

Most patients with indolent NHL (n=72) had follicular lymphoma (FL). The most common forms of aggressive NHL (n=141) were diffuse large B-cell lymphoma (DLBCL; n=87) and transformed FL (n=29). Patients received a median of three prior systemic therapies (range, 1-14 therapies), including 23 patients who received prior CAR T-cell therapy, 16 of whom were evaluable.

The objective response rate was 43.8% (n=7/16) and the complete remission (CR) rate was 25.0% (n=4/16, including two with DLBCL and two with FL).

Expansion of previously administered CAR T-cells after mosunetuzumab administration was detected by quantitative polymerase chain reaction, the authors noted. CRs were “durable,” as 92.6% of patients (n=25/27) with indolent NHL achieved CR that remained in remission (median time from first CR, 5.8 months; range: 0.2-28.9 months).

The maximum tolerated dose of mosunetuzumab had not yet been reached at doses up to 1/2/60 mg.

Twelve patients (5.5%) experienced adverse events (AEs) that resulted in treatment withdrawal. Cytokine release syndrome (CRS) occurred in 28.4% of patients, most of which were grade 1 (21.1%) and occurred during treatment cycle one. Neurological AEs occurred in 44% of patients, the most common of which were headache (14.7%), insomnia (10.1%), and dizziness (9.2%).

Four patients were re-treated with mosunetuzumab after relapse, and none experienced CRS; one patient reported neurological AEs. Among patients who relapsed after CAR T-cell therapy, five (21.7%) reported CRS and eight (34.8%) reported neurological AEs. This supports “the possibility for re-treatment with mosunetuzumab,” the author concluded. 


Schuster SJ, Bartlett NL, Assouline S, et al. Mosunetuzumab induces complete remissions in poor prognosis non-Hodgkin lymphoma patients, including those who are resistant to or relapsing after chimeric antigen receptor T-cell (CAR-T) therapies, and is active in treatment through multiple lines. Abstract 6. Presented at the 2019 ASH Annual Meeting, December 8, 2019; Orlando, Florida.

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