ASH 2025 | Phase II trial of mosunetuzumab with response-driven lenalidomide augmentation in FL and MZL

Mosunetuzumab, just like the other bispecific antibodies, offers a completely new way of treating follicular lymphoma and other indolent lymphomas with a potential for curative treatment, maybe for the first time in history. So there’s obviously an enormous interest in bringing these treatments to the first line and eliminating chemotherapy, the traditional way of treating indolent B-cell lymphomas. There are several trials that have studied this approach. Our trial used a somewhat different approach. We used a response-adaptive therapy, starting patients with treatments on mosunetuzumab and then introducing lenalidomide as an immunomodulatory agent rather than a direct cytotoxic agent. So this is a low-dose lenalidomide in contrast to some other studies that are running using full-dose lenalidomide, which has significant toxicities. And our aim was also to evaluate the complete response rate at the end of treatment and see how this translates into longer-term outcomes such as PFS or the so-called POD24, the proportion of patients who would have a relapse within two years of completing this treatment, and see if there are indicators that this could potentially improve patients’ outcomes, as well as potentially study the actual immune function on this treatment to see if these promises of immune-driven deep remissions can be attained. We enrolled 52 patients. We enrolled both patients with follicular lymphoma and marginal zone lymphoma, as we think that there is an unmet need in bringing more efficacious immunotherapy for this population as well. We have observed 82% complete response rates in the enrolled patients, and so far very few relapses, although we definitely had seen some patients who relapsed after treatment, as well as some patients who progressed during therapy. This was often in the setting of occult histologic transformation. We performed minimal residual disease analysis, finding then 93% of studied patients who were in clinical complete response also had undetectable MRD based on the ctDNA assay. And so far, our estimate of POD24 and progression-free survival, which is really attainable at 18 months right now, is about 83%. So it does look like this treatment is at least equivalent in outcomes to historical chemoimmunotherapy. It is probably not dramatically better from that specific perspective. But if you think about the toxicities and the impact on patients’ quality of life, we still think that it holds an advantage. So I hope that this strategy of starting with mosunetuzumab and then using some immunomodulation during therapy, particularly in periods where immune function may be somewhat exhausted from continuous stimulation, is something worth exploring. Even though most trials, actually, I use full doses of treatments and reserve response adaptation only to decision points based on the response at the end of treatments with regard to maintenance and other aspects.

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