European Commission Approves Mosunetuzumab for Patients with R/R Follicular Lymphoma


The European Commission has granted a conditional marketing authorization to mosunetuzumab for the treatment of adult patients with relapsed or refractory follicular lymphoma who have previously received at least 2 prior systemic therapies

Conditional marketing authorization has been granted to the CD20xCD3 T-cell engaging bispecific antibody mosunetuzumab (Lunsumio) by the European Commission for the treatment of adult patients with relapsed or refractory follicular lymphoma who have previously received at least 2 prior systemic therapies, according to Roche.1

The basis of the approval is supported by findings of the phase 1/2 GO29781 trial (NCT02500407), which met its primary end point of complete response (CR) per independent review facility (IRF) assessment in 2021, with the bispecific antibody eliciting a CR rate of 60% (95% CI, 49%-70%) at a median follow-up of 18.3 months.

Further data revealed the overall response rate (ORR) achieved with the agent to be 80% (95% CI, 70%-88%), and that the median duration of response (DOR) was 22.8 months (95% CI, 9.7–not estimable [NE]). Along with this, favorable tolerability was seen in patients with heavily pretreated follicular lymphoma who received mosunetuzumab.

“We are delighted that Lunsumio is the first bispecific antibody approved in Europe for people with relapsed or refractory follicular lymphoma,” said Levi Garraway, MD, PhD, Roche’s chief medical officer and head of global product development, in the press release. “Lunsumio’s high response rates, off-the-shelf availability, and initial outpatient administration could transform how advanced follicular lymphoma is treated.”

Within the multicenter, open-label, dose-escalation, and dose-expansion trial, mosunetuzumab was examined in patients with follicular lymphoma with grade 1 to 3a disease.2

Eligibility in the trial was open to patients with an ECOG performance status of 0 to 1 and to those who had previously received 2 or more systemic regimens, including at least 1 anti-CD20 antibody and 1 alkylating agent.

Every 3 weeks, as part of 21-day cycles through a step-up dosing approach in cycle 1, patients (n = 90) were administered mosunetuzumab. Within the first cycle, patients received mosunetuzumab at a dose of 1 mg on day 1, 2 mg on day 8, and 60 mg on day 15. For cycle 2, mosunetuzumab was given at a dose of 60 mg on day 1. In subsequent cycles, the bispecific antibody was given at 30 mg on day 1. For the patients who achieved a CR following cycle 8, they were subjected to 17 cycles of treatment. Additionally, there was no mandatory hospitalization for participants given the initial dose.

The primary end point of the trial was CR rate per IRF assessment, evaluated in comparison with the historical CR rate of 14%, and secondary end points included ORR, DOR, progression-free survival (PFS), safety, and tolerability.

Of those enrolled in the study, the median age was 60 years (range, 29-90) with 61.1% being male. Patients with an ECOG performance status of 0 made up 58.9% of the participants while 41.1% had a status of 1. A total of 23.3% of patients had stage I-II Ann Arbor disease, and 76.7% had stage III-IV disease. Additionally, those enrolled in the trial mostly had received 3 prior lines of therapy (range, 2-10), and all patients had previously received anti-CD20 therapy and an alkylator.

Other prior systemic therapies patients received consisted of PI3K inhibitors (18.9%), immunomodulatory drugs (14.4%), and chimeric antigen receptor (CAR) T-cell therapy (3.3%). Patients who had previously had autologous stem cell transplant made up 21.1% of participants.

Moreover, 68.9% of individuals were refractory to the last prior therapy they received, 78.9% of patients were refractory to a previous anti-CD20 therapy, and 53.3% were double refractory to an anti-CD20 therapy as well as an alkylating therapy. A total of 52.2% of patients also had progression of disease within 24 months (POD24) of starting treatment.

Data presented at the 2021 ASH Annual Meeting revealed that mosunetuzumab had an investigator-assessed CR rate of 60% (95% CI, 49%-70%), and the CR rates produced with the agent in high-risk subgroups were similar to that of the overall study population.

Patients younger than 65 years of age (n = 60) had a CR rate with the bispecific antibody of 55% (95% CI, 42%-68%) compared with a CR rate of 70% (95% CI, 51%-85%) in patients aged 65 years or older (n = 30). With the agent, the CR rate was 74% (95% CI, 56%-87%) for those who previously received 2 lines of therapy (n = 34) and 52% (95% CI, 39%-65%) in patients who received 3 or more prior lines (n = 56). Patients who were relapsed or refractory to their last prior therapy (n = 62) and in those who were not (n = 28) demonstrated CR rates of 52% (95% CI, 39%-65%) and 79% (95% CI, 59%-92%), respectively.

Mosunetuzumab also produced a CR rate of 50% (95% CI, 35%-65%) in the group of individuals who were double refractory (n = 48) vs 71% (95% CI, 55%-84%) in those who were not. Further, the CR rate was shown to be 57% (95% CI, 42%-72%) for those with POD24 disease (n = 47) compared with 63% (95% CI, 47%-77%) in those who did not progress within 24 months (n = 43).

Median time to response was 1.4 months (range, 1.1-8.9), and the median time to first CR was 3.0 months (range, 1.1-18.9). The median PFS with mosunetuzumab was 17.9 months (95% CI, 10.1-NE).

In regard to safety, cytokine release syndrome (CRS) was the most common toxicity, which was observed in 39% of patients. Still, CRS was low grade with 14% of patients experiencing grade 2 CRS, and it was resolved by treatment completion. Other frequently observed adverse effects included neutropenia, hypophosphatemia, pyrexia, and headache.

Two phase 3 clinical studies are exploring the use of mosunetuzumab in the second-line setting: CELESTIMO (NCT04712097), investigating mosunetuzumab plus lenalidomide (Revlimid) for patients with follicular lymphoma, and SUNMO (NCT05171647), investigating mosunetuzumab plus polatuzumab vedotin (Polivy) for patients with diffuse large B-cell lymphoma.

“Having additional treatment options for people with follicular lymphoma, where multiple prior lines of therapy have failed, is critical to help them achieve better outcomes,” Elizabeth Budde, MD, PhD, a hematologic oncologist and associate professor at the City of Hope Comprehensive Cancer Center, added in the press release. “It is exciting to have a new class of immunotherapy like Lunsumio, offering a readily available, chemotherapy-free and fixed-duration treatment, with great potential to provide durable remissions without the need to stay on treatment continuously.”

  1. European Commission approves Roche’s first-in-class bispecific antibody Lunsumio for people with relapsed or refractory follicular lymphoma. News release. Roche. June 8, 2022. Accessed June 9, 2022.
  2. Budde EL, Sehn LH, Matasar M, et al. Mosunetuzumab monotherapy is an effective and well-tolerated treatment option for patients with relapsed/refractory (R/R) follicular lymphoma (FL) who have received ≥2 prior lines of therapy: pivotal results from a phase I/II study. Presented at: 2021 ASH Annual Meeting and Exposition; December 11-14, 2021; Atlanta, GA. Abstract 127.
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