Studies demonstrating high response rates and manageable safety profiles, along with FDA approvals, have supported bispecific antibodies as promising treatment options for follicular lymphoma.
At the start of 2023, a new option became available with the accelerated approval of mosunetuzumab (Lunsumio) late last year. The first-in-class bispecific monoclonal antibody works by inducing CD20-directed CD3 T-cell engagement and is indicated for patients with relapsed/refractory disease following two or more prior lines of therapy.
Approval was based on results from the , a single-arm, multicenter, phase II study involving 90 patients who had progressive follicular lymphoma after at least two prior therapies, including an anti-CD20 monoclonal antibody and an alkylating agent.
The primary analysis showed that mosunetuzumab led to objective responses in 80% of the study population, including complete responses in 60%. After a median follow-up of 14.9 months, the median duration of response was 22.8 months, while estimated response rates at 12 and 18 months were 62% and 57%, respectively.
The FDA also granted accelerated approval to glofitamab (Columvi) for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified or large B-cell lymphoma caused by follicular lymphoma, after two or more lines of systemic therapy.
This approval was based on results from the phase I/II NP30179 study, which were presented at last year's American Society of Hematology annual meeting and simultaneously published in the .
Glofitamab was given to all patients in a fixed course for 8.5 months. More than half of patients achieved an overall response, and 43% achieved a complete response. Slightly more than two-thirds of those who responded continued to respond for at least 9 months, with a median duration of response of 18.4 months.
In other promising news, the FDA accepted for priority review the to treat adult patients with relapsed/refractory follicular lymphoma or DLBCL, which was supported by the and studies.
The phase II ELM-2 study included patients with grade 1-3a disease who were relapsed or refractory after two or more prior lines of therapy, including an anti-CD20 antibody and an alkylator. Patients were treated with a step-up regimen of odronextamab in the first cycle to help mitigate the risk of cytokine release syndrome (CRS) before receiving the full dose of 80 mg.
Investigators reported that among 121 evaluable patients, the overall and complete response rates by independent central review were 82% and 75%, respectively, with rates consistent across high-risk subgroups. The median duration of complete response was 20.5 months, median progression-free survival (PFS) was 20.2 months, and median overall survival (OS) was not reached.
The most common adverse event was CRS; two-thirds of the cases were grade 1. There were no grade 4 or 5 CRS cases, and investigators reported that the incidence of both grade 2 and grade 3 CRS was reduced with the modified step-up regimen when compared with the original regimen.
The PDUFA action date has been set for March 31, 2024.
The FDA also for the treatment of adult patients with relapsed/refractory follicular lymphoma after two or more therapies. This action was supported by data from the phase I/II EPCORE NHL-1 clinical trial evaluating the safety and preliminary efficacy of subcutaneous epcoritamab in 128 patients with relapsed, progressive, or refractory CD20-positive mature B-cell non-Hodgkin's lymphoma, including follicular lymphoma.
Meanwhile, in the phase I/II , researchers found that adding epcoritamab to rituximab (Rituxan) and lenalidomide (Revlimid) resulted in deep and durable remissions in patients with relapsed/refractory follicular lymphoma.
In a pooled analysis of this trial, the overall response rate was 98% and the complete metabolic response rate was 87%, with antitumor activity seen across subgroups, including those deemed high risk.
The most common treatment-emergent adverse events were CRS and neutropenia. CRS events were mostly low grade, all resolved, and none led to discontinuation.
PI3K Inhibitor Exits Market
In other news this year, Bayer announced plans to pull the follicular lymphoma drug copanlisib (Aliqopa) from the U.S. market following the failed confirmatory CHRONOS-4 study, and after discussions with the FDA.
The FDA had granted accelerated approval to copanlisib in 2017 based on tumor shrinkage data from the phase II CHRONOS-1 trial. In that single-arm study, the PI3K inhibitor induced responses in 59% of patients, including complete responses in 14%, with a median duration of response of 12.2 months.
In the subsequent phase III CHRONOS-3 trial, adding copanlisib to rituximab improved PFS over rituximab alone in relapsed indolent non-Hodgkin's lymphoma, including patients with follicular lymphoma. However, showed no significant OS benefit in either the overall population or the follicular lymphoma subgroup.
In adding copanlisib to standard immunochemotherapy failed to improve PFS in relapsed follicular lymphoma over immunochemotherapy alone.
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