Dr L. Elizabeth Budde: Mosunetuzumab Is Effective, Well Tolerated in R/R FL

L. Elizabeth Budde, MD, PhD, oncologist and associate professor at City of Hope, discusses the use of mosunetuzumab in patients with relapsed/refractory follicular lymphoma (R/R FL) who have received 2 or more prior lines of therapy and addresses potential cost-related implications of the drug compared with CAR T-cell therapy.

Findings presented at the 63rd Annual American Society of Hematology Meeting and Exposition (ASH 2021) showed mosunetuzumab was effective and had a manageable safety profile in patients with relapsed/refractory follicular lymphoma who have received 2 or more prior lines of therapy, said L. Elizabeth Budde, MD, PhD, oncologist and associate professor at City of Hope.

Budde is lead author of the abstract, “​​Mosunetuzumab Monotherapy Is 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: Pivotal Results From a Phase 1/2 Study.”


Can you speak on the expanded phase 1/2 results presented at ASH 2021 on mosunetuzumab for patients with relapsed/refractory follicular lymphoma (FL)?

So, in our study, the pivotal phase 2 trial, using mosunetuzumab as a monotherapy for patients with follicular lymphoma who had at least 2 prior lines of therapy, we actually restricted these patients to needing to have at least 1 anti-CD20 therapy and an alkylating agent.

The majority of patients in our study—a total of 90 of them—most of them were double refactory, and also most of them were refractory to prior lines of anti-CD20 therapy. More importantly, more than half of the patients had POD24. POD24 is what we call a subset of patients with follicular lymphoma who had initial treatment but subsequently relapsed or [became] refractory within 24 months of initial treatment. These patients are historically known to be very difficult to manage, and they have follicular lymphoma with very aggressive and poor prognosis.

In our study, the 90 patients are treated regardless of if they have POD24—regardless of any of those historical poor factors—they all responded the same. The overall response rate is 80% and the CR [complete response] rate is 60%, and it does not matter what kind of risk factors they have. So this is quite convincing, and I think it's a good statement to support the different mechanisms of action and the power of immunotherapy to overcome the resistance of the follicular lymphoma cells to otherwise conventional treatment.

Can you speak on the potential of mosunetuzumab as a cost-effective option for patients with relapsed/refractory FL prior to CAR T-cell therapy consideration?

It's not clear with mosunetuzumab—once it's approved, which I hope will be early next year—what the price tag will be. But given the different delivery route, meaning that mosunetuzumab is off the shelf, it’s available immediately and there's no involvement of ex vivo manufacturing, no cell expansion, and there's also no requirement of lymphodepletion, which is part of the CAR [chimeric antigen receptor] T-cell therapy.

In addition to this note, with its manageable safety profile, I suspect the cost of mosunetuzumab will be lower than CAR T-cell therapies—but it's given in multiple cycles. So, 8 cycles for patients who achieve complete remission, and it can be given up to 17 cycles for patients who are not in remission; for example, a patient with stable disease or a patient with a partial response.

So, it's difficult for me as a researcher and clinician to really map out the exact comparison between these 2, but I think there's definitely an advantage of giving mosunetuzumab in the community setting. I hope the cost associated with mosunetuzumab will be very reasonable.

What are some next steps following these findings presented at ASH?

We're very excited actually following this presentation ASH. Now the focus is really to continue to optimize the way we give mosunetuzumab. Instead of given intravenously, we’re testing mosunetuzumab given subcutaneously to see if we can further reduce the incidence of cytokine release syndrome and make it even safer.

Of course, we're also testing mosunetuzumab in combination with lenalidomide. This is also in patients with relapsed/refractory follicular lymphoma. And we know [the] rituximab and lenalidomide combination is a good regimen that can also benefit multiple patients. So therefore, a phase 3 study is now comparing mosunetuzumab in combination with lenalidomide vs rituximab in combination with lenalidomide. It’s being conducted in patients with relapsed/refractory follicular lymphoma.

The goal is really to try to further improve the overall response rate, complete response rate, as well as the original response and maintain the safety profile. In addition to further testing of mosunetuzumab in follicular lymphoma, the use of mosunetuzumab either alone or in combination with other drugs—for example, polatuzumab—in patients with aggressive B-cell lymphoma or mantle cell lymphoma with various stages of disease in a setting up front or in a relapsed/refractory setting are actively ongoing.

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