Mosunetuzumab induces deep and durable remissions in 3L R/R follicular lymphoma

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Published: 11 Dec 2021
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Prof Elizabeth Budde - City of Hope, Duarte, USA

Prof Elizabeth Budde speaks to ecancer about the pivotal results from a phase I/II Study investigating mosunetuzumab monotherapy as an effective and well-tolerated treatment option for patients with relapsed/refractory (R/R) follicular lymphoma (FL) who have received ≥2 prior lines of therapy.

Initially, she talks about the background of the study.

Prof Budde says that the primary endpoint was a complete response rate by PET/CT assessed by an independent review facility (IRF) using standard response criteria.

Prof Budde then discusses the methodology and key results. Mosunetuzumab induces deep and durable remissions in 3L+ R/R FL patients. High response rates are achieved and maintained for ≥12 months in the majority of patients.

Prof Budde mentions that mosun has a manageable safety profile, with C1 step-up dosing effectively mitigating CRS, enabling treatment without mandatory hospitalisation.

She concludes by mentioning that more chemo-free therapy trends can be seen currently and explains the efficacy of CAR-T cells versus immunotherapy for the treatment of these patients.

See the news story here.

ecancer's filming has been kindly supported by Amgen through the ecancer Global Foundation. ecancer is editorially independent and there is no influence over content.

The background of my study is testing mosunetuzumab as a monotherapy for patients with relapsed/refractory follicular lymphoma who had at least two prior lines of therapy. The goal is really to see whether we can improve the treatment efficacy and longer durable remissions in these patients who otherwise have much poorer outcomes.

As we know, follicular lymphoma is a lymphoma that is not curable with conventional chemotherapy and follicular lymphoma when it gets subsequent lines of therapy the response rate and duration of response get shorter and shorter. Patients with poor risk prognoses and double refractory disease, these patients are considered very high risk and usually they don’t respond well to conventional therapy.

This study is a phase II pivotal trial testing mosunetuzumab, which is a bispecific antibody using T-cells through a CD3 engagement. So basically it involves an engaged T-cell with [??] to eliminate CD20 positive malignant B-cells.

The key finding of the study is that the study actually met its primary endpoint, meaning that the overall response was 80%. The complete response rate is 60% which is significantly higher than the historical control of 14% complete response rate. So that’s the key finding. Other important findings of the study are patients when they’re getting mosunetuzumab treatment it’s a fixed duration treatment, meaning patients, if they are in complete remission, will complete eight cycles of treatment. If they are not in remission with partial response or stable disease they will complete a total of 17 cycles of treatment. So there is an endpoint.

Also, for the treatment, there is no mandatory hospitalisation stay so this regimen can be given as an outpatient and the safety profile of using mosunetuzumab monotherapy in this patient population seems to be very manageable. The side effects are very manageable – only 4.4% of patients discontinued treatment and 2.2% of them are due to mosunetuzumab. Most of the cytokine release syndrome occurred in cycle 1 and most of them are low grade. Only one patient had grade 3, one patient grade 4, and most of them confined to cycle 1 and all events actually resolved.

How can these results impact the future treatment of follicular lymphoma?

That’s a very good question. This brings another very promising off-the-shelf outpatient therapy to these patients who are in the relapsed/refractory setting. We hope the treatment will get FDA approval soon, which we are still waiting, but it will really provide a benefit to patients who otherwise do not respond well to chemotherapy or other targeted therapies.

How does this treatment option compare to CAR T-cell therapy?

CAR T-cell therapy is also for patients with follicular lymphoma in the relapsed/refractory setting and both of these treatments can complement each other pretty well. There are some distinct features of using mosunetuzumab which are it’s readily available because it’s off the shelf and it’s a fixed duration of treatment and can be given in the outpatient setting. There is really no waiting time for leukapheresis, manufacturing the product, so there is the logistical issue associated with CAR T-cell therapies but it’s really not a concern for bispecific therapies.

Follicular lymphoma patients, the trend is going towards more chemo-free therapy so bispecific antibody which is a pure immunotherapy is quite attractive. Looking at the side effect profile, we see very tolerable, manageable side effects; neurologic toxicities were all low grade with no high grade at all and less than 5% of patients experience that. This all compares very favourably to CAR T-cell therapy.

CAR T-cell therapy has a lymphodepletion which is a chemotherapy component so it’s a chemotherapy plus immunotherapy. Although CAR T-cell therapies are quite powerful, as we know there is a very high response rate, and duration of response is also quite long which, for certain patient populations, they could benefit from both CAR T-cells and bispecific antibody treatment. For patients who are unfit or for patients with logistic problems, patients who desire a complete chemo-free regimen, bispecific antibodies might be more desirable.