Long-term 3-year follow-up of mosunetuzumab in relapsed or refractory follicular lymphoma after ≥2 prior therapies

Abstract

Mosunetuzumab, a CD20×CD3 T-cell engaging bispecific antibody, redirects T cells to eliminate malignant B cells. We present updated efficacy and safety data of a pivotal phase 1/2 study after a median follow-up of 37.4 months in 90 patients with relapsed/refractory (R/R) follicular lymphoma (FL) and ≥2 prior lines of therapy treated with fixed-duration mosunetuzumab. Investigator-assessed complete response (CR) rate and objective response rate were 60.0% (95% confidence interval [CI], 49.1-70.2) and 77.8% (95% CI, 67.8-85.9), respectively. Among 70 responders, median duration of response was 35.9 months (95% CI, 20.7 to not estimable [NE]). Among 54 patients who achieved CR, 49 remained in CR at the end of treatment; median duration of CR was not reached (NR; 95% CI, 33.0 to NE); Kaplan-Meier-estimated 30-month remission rate was 72.4% (95% CI, 59.2-85.6). Estimated 36-month overall survival (OS) rate was 82.4% (95% CI, 73.8-91.0); median OS was NR (95% CI, NE to NE). Median progression-free survival was 24.0 months (95% CI, 12.0 to NE). Median time to CD19+ B-cell recovery was 18.4 months (95% CI, 12.8-25.0) after 8 cycles of mosunetuzumab treatment. No new cytokine release syndrome events or fatal, serious, or grade ≥3 adverse events were reported. With extended follow-up, mosunetuzumab demonstrated high response rates, durable remissions, and manageable safety with no long-term concerns. This supports outpatient mosunetuzumab administration as an off-the-shelf, fixed-duration, safe, and effective treatment for patients with R/R FL, including those with high-risk disease. This trial was registered at www.clinicaltrials.gov as #NCT02500407.

Graphical abstract

Figure 1.

DOR, DOCR, PFS, and OS. KM estimates showing DOR in responders (n = 70) (A), DOCR in complete responders (n = 54) by INV assessment (B), and PFS (N = 90) (C), and OS (N = 90) in the intent to treat population (D). CCOD: 2 May 2023.

Figure 2.

DOCR, PFS, and OS in patients (n = 49) with a CR at EOT. KM estimates showing DOCR (A), PFS (B), and OS (C). CCOD: 2 May 2023.

Figure 3.

Best overall response by baseline tumor mutation status. Distribution of patients by CR, PR, stable disease, or PD according to wild-type or mutational status of EZH2, TP53, BCL2, CREBBP, KMT2D, and TNFRSF14. CCOD: 2 May 2023. Mut, mutated; SD, stable disease; WT, wild-type.

Figure 4.

CD19⁺ B-cell depletion and recovery kinetics. (A) The proportion of patients and corresponding CD19⁺ B-cell counts in complete responders at specified time points during treatment and follow-up. The median time to B-cell recovery was defined as ≥5 cells per μL as determined by time to event analysis. The median time to recover to the lower level of normal was defined as ≥70 cells per μL. B-cell recovery from the time of last treatment cycle in patients with a CR is shown at a cutoff of ≥5 cells per μL (B) and ≥70 cells per μL (C). CCOD: 2 May 2023.