At the 65th ASH Annual Meeting in San Diego, California, Lorenzo Falchi, MD, Memorial Sloan Kettering Cancer Center, New York, New York, shares results from a phase 2 multicenter study which indicated that subcutaneous mosunetuzumab as first-line therapy demonstrated highly efficacious outcomes and manageable safety among patients with high-tumor burden follicular lymphoma, including those with high-risk disease. 

Dr Falchi noted that follow-up is required to properly assess the durability of responses. 

Transcript:

I am Lorenzo Falchi and I'm a lymphoma [specialist] attending Memorial Sloan Kettering Cancer Center in New York City. This year at ASH I was very excited to present the first results of our multicenter investigator-initiated phase 2 trial of subcutaneously administered mosunetuzumab for patients with newly diagnosed follicular lymphoma. 

For a very long time---over 2 decades now---the standard of care for patients with newly diagnosed high-burden follicular lymphoma has been traditional cytotoxic chemotherapy plus anti-CD20 antibodies. That hasn't really changed since the early 2000s, so we wanted to explore a chemo-free option that could provide the advantage of efficacy, but also avoid some of the common shortcomings of chemoimmunotherapy. We know that up to 15% of patients are not well-served by that approach, and they relapse early after completion of chemoimmunotherapy. Also, we know that this approach is burdened by some potentially life-threatening complications, including severe infections or other cancers like leukemia, for example.

We know that the biology of follicular lymphoma is really centered on a fundamental dysfunction of the immune system, particularly the T-cell component of the immune system. We thought that redirecting T-cells against lymphoma cells could be a viable way forward to treat follicular lymphoma, [and] potentially improve patient outcomes. 
We took advantage of mosunetuzumab. Mosunetuzumab is a first-in-class CD20-CD3 bispecific antibody that can be administered subcutaneously or intravenously. It's a very active agent in follicular lymphoma in patients with recurrent disease. It produced an overall response rate of 80%, complete responses of 60%, [and] a median progression-free survival [of] close to 2 years. 

We hypothesized that using this drug in patients who were chemotherapy-naive could produce even better results and even more durable responses. For this trial, we enrolled patients with CD20-positive, low-grade follicular lymphoma [who] needed chemotherapy per what's called the [Groupe d'Etude des Lymphomes Folliculaires] (GELF) criteria. 

We administer the drug subcutaneously on a step-up dosing schedule during cycle 1, and then every 3 weeks for up to 6 months, or 8 doses, at which point we would take a response assessment and patients who were in complete response would discontinue therapy, whereas those who had a partial response were allowed to continue therapy for an additional 6 months. Patients who progressed, of course, were taken off the study. 
To date, we've enrolled 54 patients who have been dosed and they're safety evaluable. Of these [patients], 45 are also efficacy evaluable because we were able to do at least 1 imaging study in them. The follow-up for this patient population [is] just shy of 6 months. We haven't seen almost any treatment delays---5% of the entire number of patient cycles were delayed usually by just about a week. 

The characteristics of our patient populations were quite comparable with what you would see in large randomized frontline clinical trials, with the exception that we saw a relatively higher percentage of patients with follicular lymphoma grade 3A, which tends to be a more aggressive disease at a worse prognosis compared to grade 1 or 2. 

In terms of safety, the drug was very well tolerated. We administer treatment in a fully outpatient setting, and the main 2 adverse events were injection site reactions, which is commonly seen with subcutaneously administered bispecific antibodies as well as CRS, or cytokine release syndrome. This was seen in 58% of patients, but it was really of grade 1 in all cases except 2. We did not admit patients for the management of CRS except in cases of grade 2 CRS. 

We used extra corticosteroids in just about 20% of the patients and only 2 patients required tocilizumab. Other notable adverse events included infections---generally mild upper respiratory infections for the most part---liver number elevations, and skin rash. 

But, coming to efficacy, that's the part where we were the most excited. Out of those 45 patients [who] were evaluable, an impressive 96% achieved an objective response, and 76% of those patients had a complete metabolic response by Lugano criteria. This was a finding that we weren't necessarily expecting, but we were very happy to see th[at] responses were very consistent across high-risk subgroups. That includes patients with bulky disease, patients with follicular lymphoma of grade 3A and patients with elevated [standardized uptake value] (SUV) at baseline. So, very consistent efficacy profile of mosunetuzumab single agent. 

An additional encouraging finding was that most of those complete responses were maintained after treatment was discontinued. As I said before, this is a time-limited therapy. We were treating patients for up to 6 months and then discontinued therapy, which is a very valuable treatment strategy in patients who may need treatment for many years. I think we really learned that subcutaneously administer[ing] mosunetuzumab as a time-limited, easy-to-deliver therapy was highly efficacious in patients with newly diagnosed high burden follicular lymphoma. This is a chemo-free approach that has response rates that are comparable to what you could see with chemoimmunotherapy. So, it does offer hope for patients, particularly the younger ones, where the use of chemotherapy can be especially challenging in the long term. The safety profile of mosunetuzumab in this study was very reassuring. 

We did not see any unexpected adverse events, [which] is really similar to what we did see in the pivotal phase 2 trial in patients with relapsed or refractory disease. It's possible that subcutaneous administration reduces the severity and the incidence of some adverse events, including CRS compared to the intravenous formulation. Clearly, we'll need more patients to A, understand the durability of responses, and B, solidify the safety profile on a larger scale. But clearly, our results support further exploration of mosunetuzumab and patients with newly-diagnosed follicular lymphoma in need of therapy.

Source: 

Falchi L, Okwali M, Ghione P, et al. Subcutaneous (SC) mosunetuzumab (mosun) as first-line therapy for patients (pts) with high tumor-burden follicular lymphoma (FL): First results of a multicenter phase 2 study. Presented at the ASH 65th Annual Meeting & Exposition; December 9-12 2023; San Diego, California. Abstract 604