Mosunetuzumab monotherapy continues to show promising efficacy with durable responses and manageable safety with at least 1 year of follow-up for patients with diffuse large B-cell lymphoma (DLBCL) who are elderly or unfit for standard first-line chemoimmunotherapy. 

Currently there is a need for less toxic, efficacious alternative treatments for patients with DLBCL who are unable to tolerate the full dose of standard chemoimmunotherapy due to age or pre-existing comorbidities. The CD20/CD3 T-cell-engaging bispecific monoclonal antibody mosunetuzumab has previously shown promising efficacy as a monotherapy in this patient population, in a phase ½ study. The current data includes updated efficacy and safety outcomes from that study, with ≥1 year of follow-up from the end of treatment.

These results were presented by Adam Olszewski, MD, Brown University, Providence, RI, at the 2022 American Society for Hematology (ASH) Annual Meeting & Exposition in New Orleans, LA.

The trial enrolled patients with DLBCL aged either ≥80 years, or 60 to 79 years with ≥1 activity of daily of living or instrumental activity of daily living impairment; or reduced cardiac, renal, or liver function preventing treatment with full-dose chemoimmunotherapy. This study used a step-up dosing regimen where mosunetuzumab was administered intravenously in 21-day. 

Patients received 1 mg mosunetuzumab on day 1 of the first cycle, 2 mg on day 8, 13.5 mg or 30 mg on day 15 and on day 1 of each subsequent cycle. At cycle 8, patients with a complete response stopped treatment. Patients with a partial response on stable disease continued treatment for up to 17 cycles. The 2 safety-evaluation cohorts received the 1/2/13.5 mg regimen of mosunetuzumab (n = 8), while patients in the expansion phase received the 1/2/30 mg regimen (n = 46). Primary end point for the trial included objective response and complete response rates. These results include combined data from both dose regimens.

As of June 1, 2022, the median duration of follow-up was 23.3 months and the median number of cycles received was 8. Of the 54 patients, the best overall response rate was 56%, with a complete response rate of 43%. The median duration of complete response was 15.8 months (95% confidence interval [CI], 8.5 to not estimable). Of the 23 patients who achieved a complete response at any point, 11 patients maintained the complete response for >12 months. The 12-month progression-free survival rate was 39% (95% CI, 25.8 to 52.8).

Grade 3/4 adverse events were observed in 48% of patients. The most common treatment-emergent adverse events, occurring in >10% of patients, were rash (31%), cytokine release syndrome (CRS; 26%), and fatigue (26%). There were 10 patients with grade 1 CRS and 4 patients with grade 2 CRS. There were no cases of a grade ≥3 case of CRS, and no new instances of CRS have been reported since the previous cut-off. There were no cases of ICANS related to mosunetuzumab observed. One patient discontinued treatment due to an adverse event (renal failure not attributed to mosunetuzumab). Of the 3 deaths that occurred, none were considered mosunetuzumab-related (1 due to natural causes, 2 due to COVID-19 pneumonia).

Dr Olszewski and colleagues wrote, “These data support a potential future role for [mosunetuzumab] in elderly/unfit patients with previously untreated DLBCL.”

Source:

Olszewski A, Avigdor A, Babu S, et al. Mosunetuzumab monotherapy continues to demonstrate promising efficacy and durable complete responses in elderly/unfit patients with previously untreated diffuse large B-cell lymphoma. Presented at the ASH Annual Meeting & Exposition; December 10-13, 2022; New Orleans, LA, and virtual. Abstract 738.