ICML 2025 | The value of bispecific antibodies in FL: current perspectives & ongoing studies with these agents

So follicular lymphoma is a chronic indolent disease that by most accounts is considered non-curable, but it’s also a disease where the natural course and the treatment history tend to be very long. So strategy matters, positioning of different drugs matters, and I think bispecific antibodies have been a really transformative class of drugs for these patients because they’re largely administered on an outpatient basis. They’re very potent. And I would call them paradigm-shifting because we’re used to thinking that with subsequent lines of therapy, the chance of a response to treatment and the duration of response to that treatment tend to go down over time. With T-cell-based immunotherapy, including bispecific antibodies, what we have seen is an inversion of this paradigm where we now have longer duration of response and higher rates of response in patients who were very heavily pre-treated after three, four, five lines of therapy. Clearly, that was the initial enthusiasm of the studies of mosunetuzumab, for example, or epcoritamab, both of which are approved for the treatment of recurrent follicular lymphoma. But that also stimulated the appetite for maximizing their potential and extracting more potential from these agents by combining them with other drugs. The natural partner for both of these drugs has been lenalidomide because lenalidomide in combination with rituximab is already an approved regimen in patients with recurrent follicular lymphoma. So combining mosunetuzumab with lenalidomide or epcoritamab with lenalidomide and rituximab has been sort of a natural next step. And the preliminary results from both studies in patients with follicular lymphoma after at least one line of therapy have been incredibly exciting, especially those for rituximab, lenalidomide, and epcoritamab, where among 111 patients, the overall response rate was 96% and the complete metabolic response rate was 86%, close to 87%. So there clearly is a potential for a paradigm-shifting there, and certainly, those studies have supported the currently ongoing Phase III randomized trials that are comparing these combinations against simple rituximab and lenalidomide. So if any of these studies are positive, that could establish a new standard of care in relapsed follicular lymphoma. Clearly, the enthusiasm didn’t stop there, so these drugs have been tested in the frontline setting. We have put together and presented a Phase I study of mosunetuzumab in patients with newly diagnosed follicular lymphoma, the MITHIC-FL1 study. There’s another trial combining epcoritamab and rituximab plus lenalidomide in frontline, which we also developed and presented recently at meetings. And both of these studies, in addition to mosunetuzumab plus lenalidomide as a frontline option, have formed the basis of two of several large ongoing randomized trials comparing bispecific-based combinations to the currently accepted standard of care, which is traditional chemoimmunotherapy for patients with newly diagnosed follicular lymphoma. That includes the odronextamab combination study. That includes the AZD0486, or SURO for short, study, alongside with the mosunetuzumab and the epcoritamab study. So we’re going to have a plethora of studies, including hundreds if not thousands of patients, trying to establish potentially a new standard of care, which would be a chemo-free standard of care. So we could call this era the era where immunotherapy has a second chance at challenging the role of traditional chemotherapy for patients with follicular lymphoma.

This transcript is AI-generated. While we strive for accuracy, please verify this copy with the video.