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Expert Highlights Early Efficacy Seen With Mosunetuzumab in Follicular Lymphoma and DLBCL

Danielle Ternyila
Published Online:7:48 PM, Wed February 27, 2019
Elizabeth Lihua Budde, MD, PhD
Elizabeth Lihua Budde, MD, PhD
Patients with relapsed/refractory B-cell indolent lymphomas were treated with mosunetuzumab in a phase I/Ib trial, with findings showing promising overall response rates (ORR) and complete responses (CR) among patients with follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL).

Mosunetuzumab was administered to patients via a dose-escalation schedule of either 1 dose every 3 weeks in group A or 1 dose every week in group B, followed by 1 dose every 3 weeks after the first cycle. While adverse events (AEs) occurred on day 1 regardless of the dose, this schedule allowed for further dose escalation without increasing the toxicities.

In patients with relapsed/refractory FL, the ORR was 69.2% across doses of mosunetuzumab and the CR rate was 38.5%. In patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) or transformed follicular lymphoma, the ORR was 34% and the CR rate was 19.1% across dose levels.

“In this clinical trial…the treatment is different than in other clinical trials in that the patient will only receive a limited [number of] cycles of treatment,” said Elizabeth Lihua Budde, MD, PhD. “I think this is important because no one wants to be on treatment for a long time, and we are encouraged by the durability of response.”

In an interview with Targeted Oncology during the 2018 ASH Annual Meeting, Budde, an assistant professor at City of Hope, discussed the results seen from this trial for patients with FL and DLBCL. She shared plans for the next steps and how this treatment may impact the patient population.

TARGETED ONCOLOGY: Can you give us some background to this trial?

Budde: Mosunetuzumab is a first-in-human CD3/CD20 bispecific antibody. It’s an immunotherapy being tested in this phase I/Ib clinical trial for patients with relapsed/refractory DLBCL or FL and mantle cell lymphoma. 

TARGETED ONCOLOGY: How was the trial designed?

Budde: This trial is a phase I design and has dose escalations in group A, so 1 dose every 3 weeks for up to 8 cycles for the initial treatment, and group B, which is after we learned about the schedule, toxicity and responses, is now open. Group B, in the first cycle, is 1 dose every week with dose escalation, so day 1 is a lower dose, day 8 is a higher dose, and day 15 is the highest dose. For cycle 2 and on, this goes on every 3 weeks. The reason for this dosing is because we see most of the AEs occur after day 1 regardless of the dose. By doing this dosing, it allows further dose escalation without increasing toxicity.

So far, we have treated 131 patients who are eligible based on the toxicities and safety, and we have seen encouraging response rates in patients with FL and DLBCL. 

TARGETED ONCOLOGY: Have there been any significant AEs noted with this treatment?

Budde: Most of the AEs are very mild, grade 1 and grade 2. No one had any cumulative or chronic AEs. The reason for patients to discontinue due to AEs is only seen in 4 patients, so around 3%.

TARGETED ONCOLOGY: What have the efficacy findings been so far?
 
Budde: The efficacy is very encouraging. This study is still ongoing, and we are still doing dose escalation per scheduling optimization, but so far for patients with relapsed/refractory FL in the later-line setting, we have observed a 69% overall response rate (ORR) and close to 40% complete response (CR). In patients with DLBCL, we have seen up to 40% in ORR and 19% CR. More importantly, for patients who achieve complete remission after completing 8 cycles of treatment, only 1 patient relapsed, and that patient got a second treatment and went on to a second complete remission. These patients are being followed now for at least 300 days. The longest patients, close to 2 years, still remain in remission. Those patients also include 6% of patients with prior CAR T-cell treatment. 

TARGETED ONCOLOGY: What are the next steps for this trial?

Budde: The next step is to continue the dose escalation and optimization of the scheduling. We are also actively designing and testing these bispecific antibodies with chemotherapy with checkpoint inhibitors, still an immunotherapy, with an antibody drug conjugate with a different target so we can do dual targeting. 

TARGETED ONCOLOGY: Why are these findings significant?

Budde: The main point of this treatment is it’s a novel, pure immunotherapy, and we had many patients who began the treatment in pretty poor shape with poor ECOG, but when they are on treatment, they are actually able to continue their day-to-day activities. For quite some patients, there is improvement in their quality of life. We had patients [who were] wheelchair-bound, and after a couple of cycles of treatment, the patients were able to ambulate and had pretty good daily activity.

TARGETED ONCOLOGY: What is the take-home message from this research?

Budde: The biggest takeaway is this is a novel treatment using immunotherapy to mitigate a patient’s immune cells inside the patient’s body. This drug serves as a bridge to bring together the T-cells and the patient’s own lymphoma cells. The T-cells would then be redirected, activated, and mitigated towards the lymphoma’s elimination. It’s a novel mechanism, and we have seen multiple complete remissions. It’s very encouraging. I’m hoping we will be able to treat more patients, and I’m hoping this kind of treatment will be able to move forward to an earlier line of therapy so more patients will be able to use this technology.

TARGETED ONCOLOGY: How does this clinical trial stand out among other trials in the field?

Budde: In this clinical trial, we are testing a novel treatment, and the treatment is different than in other clinical trials in that the patient will only receive a limited [number of] cycles of treatment. Initial treatment is only 8 cycles, and the patient can complete treatment and just do follow-up. We don’t treat the patient continuously until they progress or relapse. I think this is important because no one wants to be on treatment for a long time, and we are encouraged by the durability of response. If they complete treatment, there is a high chance that they will stay in remission. This has set this clinical trial apart from others.

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