Mosunetuzumab Demonstrates Favorable Efficacy and Tolerability in Relapsed/Refractory Follicular Lymphoma

Matthew Matasar, MD, Rutgers Cancer Institute, New Brunswick, NJ, discusses a phase 2 study exploring the safety and antitumor activity of fixed-duration mosunetuzumab, a CD20-CD3 T-cell-engaging bispecific monoclonal antibody, for patients with relapsed/refractory follicular lymphoma (FL).

The findings from this study were published in the Lancet Oncology, showing a favorable safety profile and high rate of complete remissions with mosunetuzumab in this patient population, supporting the potential for outpatient administration of this regimen.

Transcript:

I'm Dr Matt Matasar. I'm the Chief of Blood Disorders at the Rutgers Robert Wood Johnson Cancer Institute in New Jersey.

What led you and your coinvestigators to explore mosunetuzumab in relapsed/refractory FL? The standard of care for multi-relapsed follicular lymphoma is really quite heterogeneous in America and worldwide. We really seem to currently lack effective, safe, and durable treatments in this high-risk patient population. In that context, we evaluated the use of mosunetuzumab, which is a bispecific antibody directed against CD20 and CD3, in the treatment of multi-relapsed follicular lymphoma.

What was the design of this phase 2 study?

This is a globally conducted, single-arm phase 2 study. Truly, it has a number of different arms and aims. We've really been evaluating mosunetuzumab across the B-cell spectrum, both indolent and aggressive lymphomas. But here, we reported out our pivotal experience with follicular lymphoma in the third line and beyond.

The study included dose finding efforts, in terms of both schedule and dose, but we've landed on, what we believe is, the optimal intravenous dosing of mosunetuzumab. And then, we expanded at that dose level and schema, again, trying to optimize premedication, in order to mitigate toxicities of mosunetuzumab and to more fully characterize both the safety and activity of Mosun, in this patient population.

What were the results of this study?

At the time of reporting, we'd enrolled 90 patients with multi-relapsed follicular lymphoma, and we reported out our collective experience, not just at our ultimate dose level, which is step up dosing with weekly step up during the first cycle of 1 mg intravenous, then 2 mg, and then 60 mg cycle 1 day 15, cycle 2, day 1, again, 60 mg, and then, stepping down to 30 mg intravenously, every 3 weeks, given until 8 cycles had been administered. At the end of 8 cycles, we performed a PET scan to evaluate response.

Patients who had achieved a complete response, treatment was then discontinued and patients were followed. Patients who had not yet achieved a complete response but were deriving clinical benefit could continue on until maximum of 17 cycles had been administered.

What we found overall with mosunetuzumab at our data cutoff date with a median follow up of 18 months, we'd seen a complete response rate of 60% and an overall response rate of 80%. Certainly, these numbers compare favorably to historical controls. Furthermore, we've seen durability of response with some patients with ongoing response at 2 years and beyond.

In terms of toxicity, we do know that that mosunetuzumab does have toxicity as a T-cell engaging therapy. It does have both some immunosuppression due to [inaudible 00:03:06], as well as toxicities that one would typically associate with T-cell engaging, such as cytokine release and neurotoxicity. However, the rates of cytokine release are quite low, particularly with regards to severe cytokine release, meaning grade 3 or greater. Truly even grade two is uncommon with mosunetuzumab, and the vast majority of cytokine release phenomena that patients experience occurred during that first step up experience. And beyond cycle two, day one, cytokine release syndrome is very uncommon.

Furthermore, in distinction or in contrast to CAR T-cell therapy, neurological consequences, the so-called ICANS is very uncommon with mosunetuzumab, with no cases of severe neurological consequences from this treatment. There were no treatment related grade five events that occurred. Again, reinforcing the safety of this treatment. And treatment discontinuation or delay was uncommon. Again, supporting the conclusion that mosunetuzumab is safe and active, in this patient population.

What do you want your colleagues to know about mosunetuzumab and what to expect when considering this treatment option for patients?

What I would want to emphasize is that these results really do establish mosunetuzumab as a highly relevant option for patients with multiple relapsed follicular lymphoma. These are patients that are not ideally served by our current options, all of which have limitations. Whether limitations due to inconvenient scheduling and lack of durability, or limitations due to severe toxicity and logistical hurdles. Mosunetuzumab may represent that sweet spot of a highly active compound that can be safely administered in an outpatient setting and in community settings.

Our hope is that this is going to achieve FDA approval at the end of the year and represent a new and attractive option for physicians and patients facing multi relapsed follicular lymphoma. There will be a learning curve on giving these treatments in community settings. Although the rates of cytokine release syndrome are low, they do occur and they do require physicians to be educated and to have some degree of clinical comfort in managing low to intermediate grade cytokine release, including an understanding of the relevance of using tocilizumab and when and how to intervene with toci steroids or other modulating treatments to mitigate toxicity, should it occur.

What are the next steps for mosunetuzumab?

Even while we do anticipate, or at least hope, for FDA approval for this as monotherapy in patients with follicular lymphoma having received two prior lines of therapy or more, clearly, this is not the end of the story for Mosun. There's a lot of work ongoing to further develop and leverage its activity and safety profile, including looking at Mosun in earlier lines of therapy and indolent lymphoma.

Continuing to evaluate it in aggressive lymphoma, either as monotherapy or in combination, including studies in first line diffuse large B-cell lymphoma, combined with CHOP, first line diffuse large B-cell lymphoma for patients who are ineligible for anthracycline based chemotherapy. Combining it with pertuzumab in this high risk frail population and number of other combination settings for patients with relapsed or refractory indolent or aggressive B-cell lymphoma.

We're really still at the forefront of how best to leverage bispecific antibodies, such as mosunetuzumab, but these first results and hopefully our first approval for follicular lymphoma will really lead the way towards ongoing development of this and related compounds.

Is there anything else you would like to add?

I would just want to add that this is a really exciting time for physicians treating B-cell lymphomas and for patients facing this diagnosis. Mosun, and other bispecific antibodies, including glofitamab, epcoritamab, odronextamab, IGM-2323, and others, really do offer tremendous potential for moving this field forward and getting us tools to better improve outcomes for our patients.

Source:

Budde LE, Sehn LH, Matasar M, et al. Safety and efficacy of mosunetuzumab, a bispecific antibody, in patients with relapsed or refractory follicular lymphoma: a single-arm, multicentre, phase 2 study. Lancet Oncol. 2022;23(8):1055-1065. doi:10.1016/S1470-2045(22)00335-7