How Effective is Mosunetuzumab as a First-Time Follicular Lymphoma Treatment?

If you are a newly diagnosed patient with follicular lymphoma, how effective is the bispecific antibody mosunetuzumab (Lunsumio, Genentech) when used as a first treatment for a fixed period of time? 

This immunotherapy is currently FDA-approved for follicular lymphoma patients who have had at least two prior treatments, usually including chemotherapy for those with high-tumor burden.

What about moving mosunetuzumab to a front-line instead of a third-line treatment for people with high-burden follicular lymphoma? Bypassing chemotherapy could help reduce the negative side effects patients experience. 

Lorenzo Falchi, MD, of Memorial Sloan Kettering Cancer Center, investigated this question in phase 2 of the Mithic-FL1 trial and presented his findings at the 2024 ASH conference. 

Watch Dr. Falchi’s interview or read the study’s highlights below to learn how this important trial is paving the way to providing patients earlier access to immunotherapies and moving standard follicular lymphoma treatments away from chemotherapy. 

First-Line, Fixed-Duration Mosunetuzumab in the Mithic-FL1 Trial 

How Was Mosunetuzumab Administered?

In the study, mosunetuzumab was administered as a subcutaneous injection over the course of 8 cycles (about 6 months; each cycle was 21 days). If patients reached a complete response by that time, meaning cancer cells were not detected by testing, they would stop treatment. However, those who had only achieved a partial response (cancer cells were partially reduced) by the 8-cycle mark, continued to receive the treatment for up to 17 cycles (about 12 months).  

Usually, mosunetuzumab is administered by intravenous infusion (IV). The newly developed injection form is an attractive and convenient option for patients who don’t want to wait for an IV. Another benefit of mosunetuzumab is that patients receive it in an outpatient setting, meaning they do not have to stay in the hospital overnight. This provides patients with the flexibility they need to travel to the clinic for their treatment and then go home. 

A note about step-up dosing and pre-treatments to expect: To help reduce the risk of patients experiencing side effects, mosunetuzumab was administered by step-up dosing during the first cycle. This strategy slowly and safely increases the medication until it reaches its normal dose. 

Another strategy to reduce the risk of side effects in cycle 1 was for patients to receive pre-treatments of an antihistamine (diphenhydramine), a corticosteroid to reduce inflammation (dexamethasone), and acetaminophen. 

What Were the Results of the Mithic-FL1 Study?

Overall Response and Complete Response

In the Mithic-FL1 trial, 76 patients with high-burden follicular lymphoma received mosentuzumab treatment. The results were highly promising. The best overall response rate, indicating a partial or complete reduction of cancer cells, reached 95%. Remarkably, 80% of patients achieved a complete response, meaning their cancer was not detected by scans.  

Most patients reached a complete response within the first four treatment cycles. However, 9 patients had not achieved complete response by the 8th cycle and continued treatment up to cycle 17. Of these, 4 patients eventually achieved a complete response, either by the 17th cycle or shortly thereafter. Those who still had a partial response after cycle 17 either underwent involved-site radiation to target remaining cancer cells or were closely monitored. 

Long-Term Outcomes: Progression-Free Survival and Overall Survival

One year after starting treatment, the long-term outcomes remained very positive:

• 88% of the patients maintained progression-free survival, meaning they were alive without the cancer progressing
• The overall survival rate was 99%, with the vast majority of patients alive at this point

What Were the Side Effects of Mosunetuzumab?

The most common side effects were mild versions of injection site reactions, cytokine release syndrome, infections, muscle/joint pain, dry skin, and fatigue. Only two patients needed to be hospitalized and treated with tocilizumab (an anti-inflammatory therapy) for severe cases of cytokine release syndrome, both of whom recovered. Remarkably, no patients experienced neurotoxicity, a brain-related side effect that causes symptoms like confusion.

Key Takeaways 

The results of the Mithic-FL1 trial are very promising for people with high-burden follicular lymphoma. It shows that using the bispecific antibody mosunetuzumab as their first treatment for a set amount of time offers high odds of achieving a complete response that, for the majority of patients, lasted beyond 1 year. The therapy also has manageable side effects and can be administered in an outpatient setting as an injection, making this off-the-shelf antibody an attractive alternative to chemotherapy. 

With its promising results, Dr. Falchi’s team hopes that mosunetuzumab will undergo further trials in larger groups and potentially establish a new standard of care for follicular lymphoma treatment.

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Source: 

• Single-Agent Mosunetuzumab Produces High Complete Response Rates in Patients with Newly Diagnosed Follicular Lymphoma: Primary Analysis of the Mithic-FL1 Trial