Fixed-Duration Mosunetuzumab Yields Promising Safety, Remission Rates in Relapsed/Refractory Follicular Lymphoma

Treatment with mosunetuzumab (Lunsumio) resulted in high rates of remission and a tolerable safety profile among patients with relapsed/refractory follicular lymphoma who received 2 or more prior lines of therapy including an anti-CD20 and an alkylating agent, according to findings from a phase 1/2 study (NCT02500407).

After a median follow-up of 18.5 months, the complete response (CR) rate was 60.0% (95% CI, 49.1%-70.2%) by independent review committee (IRC), which was significantly higher than the historic control copanlisib (Aliqopa; 14%; P <.0001), meeting one of the trial’s primary end points.

The trial was conducted at 49 institutions across 7 countries. Patients were required to be at least 18 years of age with histologically confirmed disease and an ECOG performance status of 0 or 2. Patients were treated with 1 mg of mosunetuzumab on day 1, 2 mg on day 8, and 60 mg on day 15 of the first 21-day cycle; 60 mg on day 1 of cycle 2; and 30 mg on day 1 of each subsequent cycle. Complete responders received treatment for up to 8 cycles, whereas partial responders or those with stable disease continued for up to 17 cycles of treatment.

The primary end point included the CR rate by IRC and secondary end points included the investigator-assessed CR rate, objective response rate by IRC and instigator assessment, duration of response (DOR), and duration of complete response.

Investigators enrolled a total of 90 patients from May 2, 2019, through September 25, 2020. The majority of patients were men (61%) and had stage III or IV disease (77%). Investigators also reported that 69% of patients were refractory to their last therapy, 79% were refractory to a prior anti-CD20 agent, and 53% were double refractory to an anti-CD20 agent and an alkylating agent. Over half (52%) had a history of disease progression 24 months following initiation of treatment.

Patients were treated with a median of 8 cycles of mosunetuzumab and 60% of patients had completed initial treatment. Thirty-six patients discontinued treatment due to progressive disease (28%), adverse effects (AEs; 4%), physician’s choice (4%), use of a different anti-lymphoma therapy (2%), and patient withdrawal (1%). At the cut off, 2% of patients were being retreated, 84% were in follow-up, and 13% had discontinued therapy.

Nearly all patients (94%) experienced a reduction in tumor size. A total of 80.0% (95% CI, 70.3%-87.7%) of patients achieved an objective response. The median progression-free survival (PFS) was 17.9 months (95% CI, 10.1–not reached [NR]) and the 12- and 18-month PFS rates were 57.7% (95% CI, 46.9%-68.4%) and 47.0% (95% CI, 34.4%-59.6%) by IRC and 57.6% (95% CI, 46.8%-68.4%) and 51.0% (95% CI, 38.9%-63.0%) by investigator assessment, respectively.

The median duration of response by IRC was 22.8 months. Investigators estimated that 56.9% of responders and 70.2% of complete responders maintained a response at 18 months at minimum. Moreover, the median duration of CR was NR (95% CI, 14.6-NR). Both median overall survival (OS) and time to next treatment were not reached. Additionally, the event-free survival rate at 18 months was 61.0% (95% CI, 50.0%-72.0%) and the OS rate was 89.6% (95% CI, 82.5%-96.6%).

Frequent AEs included cytokine release syndrome (44%), fatigue (37%), and headache (31%) and grade 3/4 AEs included neutropenia or decreased neutrophil count (27%), hypophosphatemia (17%), hyperglycemia (8%), and anemia (8%). A total of 47% of patients experienced serious AEs. A single patient experienced a grade 5 AE of malignant neoplasm progression of follicular lymphoma.

Reference

Budde LE, Sehn LH, Matasar M, et al. Safety and efficacy of mosunetuzumab, a bispecific antibody, in patients with relapsed or refractory follicular lymphoma: a single-arm, multicentre, phase 2 study. Lancet Oncol. 2022;23(8):1055-1065. doi:10.1016/S1470-2045(22)00335-7