ICML 2025 | Safety & efficacy of mosunetuzumab with/without the addition of lenalidomide in frontline FL & MZL

Mosunetuzumab is one of the bispecific antibodies which has been developed for treatment of follicular lymphoma. It has been very successful in the relapsed/refractory setting and probably has opened a world of new possibilities for patients. We are interested in studying in first-line treatments and also extending this efficacy from follicular lymphoma to marginal zone lymphoma. These lymphomas are fairly similar to some extent biologically and in terms of the treatment patterns that have been historically used. So we thought that we could see some interesting responses as well. 

And so far it has panned out. Our trial now has almost completed enrollment at this point and we see a complete response rate of 86% with really just a few patients who have transformed disease. It was not quite recognized earlier on, but all these responses are complete otherwise. We see the similar response rates both in the setting of follicular lymphoma and marginal zone lymphoma. We are hoping to see some similarities and differences and definitely we can see some differences with specifically splenic marginal zone lymphoma patients experiencing more of the cytokine release syndrome. These patients often have extensive bone marrow and blood involvement which are the risk factors for cytokine release syndrome. But overall even these patients the toxicity is manageable with all these events being grade one and altogether, the rate of cytokine release syndrome with mosunetuzumab in the first-line setting that we see is in a range of 20-25%, which is similar to refractory disease. And all these patients were managed in a community setting in a very manageable way. 

We use lenalidomide not at full strength, but rather in our trial we added, as we call it, immune augmentation to enhance the activity of mosunetuzumab later on in the treatment. So only patients who do not attain complete response within three months of therapy receive lenalidomide. So these are smaller doses given continuously. And we have not observed any major toxicities related to lenalidomide in this setting. We definitely see patients who have, as we call it, converted from partial response to complete response with the use of this drug, but only about 25 to 30% of patients required the addition of lenalidomide. Otherwise, patients actually achieve complete responses with mosunetuzumab alone. 

So otherwise, this treatment provides a really good quality of life for patients. From my perspective, they probably would be able to say it best themselves, but they experience some fatigue and injection reactions. We use subcutaneous mosunetuzumab, so they are mostly cutaneous reactions. But they mostly dissipate within the first couple of cycles. But otherwise we have not seen any major toxicities. We had some patients who developed, interestingly, opportunistic pneumonia, pneumocystic pneumonia in the first cycle of treatment, which probably indicates some disruption in the operation of the immune system early on on treatment. But otherwise the patients have, most of them completed, have treatment. I think we only had two patients who stopped treatment early on. Otherwise a list of adverse events, mostly low-grade, with occasional higher-grade neutropenia that occurs often in the setting of viral infections or somewhat incidentally and typically resolves without any consequences. So we hope this treatment can be still developed and is both tolerable and highly efficacious in first-line setting.

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