Mosunetuzumab Led to Durable Complete Response in Majority of Patients with Lymphoma During Follow-Up Study

Stephen Schuster, MD, a physician with the University of Pennsylvania in Philadelphia, PA, joined Pharmacy Times to discuss long term follow-up data evaluating mosunetuzumab (Lunsumio; Genentech) for patients with relapsed/refractory follicular lymphoma (FL). This data was originally presented at the 65th American Society of Hematology (ASH) Annual Meeting & Exposition, which took place in December 2023 in San Diego, California.

Schuster opens up about his expectations about mosunetuzumab, where he delves into positive data regarding patient response rates and more. Schuster also discusses toxicities, toxicity management, and highlights important caveats about testing to determine whether or not a patient should receive mosunetuzumab.

PT Staff: What was theNCT02500407 pivotal study to evaluate mosunetuzumab for follicular lymphoma? What were the primary outcomes?

Stephen Schuster, MD: It's basically a 3-year follow up study. So the disease that was under study was follicular lymphoma (FL), which is considered often called a low-grade lymphoma, slow-growing lymphoma. [It’s] very responsive initially, more than two-thirds of patients…up to really more than 75% of patients [are responsive] to most therapies. But eventually, some people become resistant to the multitude of therapies that we have for this, and that's where this new drug, mosunetuzumab, a bispecific antibody, came in.

The purpose of the study was to see what kind of response rates we would get in patients with FL that were relapsed or failed to respond to a CD20 antibody and an alkylating agent, which are standard prior therapies, in combination or sequential. You had to have failed at least 2 prior therapies to be eligible for the study. For those where disease (even if you have had progression or relapse after a treatment) returns, you can oftentimes get another response, but the response become progressively shorter until it stops working.

The long-term follow-up in this study (36-month follow-up) is actually important, and it's important because the duration of response (DOR) is expected to be shorter than the response to the antecedent therapy if this agent follows the response outcome characteristics of other agents used in this setting of FL that's relapsed/refractory (r/r) after a couple of prior therapies.

The initial study was just powered by response rate, and it was really spectacular. The 60% complete response (CR) rate against historical controls, where we were in the third line, thinking down around 15 to 20%. And overall response rate (ORR) was 80%. And at the longer follow-up, which is approaching 3 years (30 months), about three-quarters of the patients are CRs. So if you look at all the patients that were treated, 60% of them have a CR and at 3 years after that CR, most of those patients— three-quarters of them— in fact, are still in CR.

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If you look at the antecedent remission durations for these patients, they were significantly shorter. But this is a novel mechanism of action. It's kind of akin to the CAR T-cell therapies that you may have heard about, these bispecific antibodies like mosunetuzumab engage the body's T lymphocytes and target them towards the tumor cells and you have a T cell directly killing the tumor cells. So this is kind of a different approach to chemotherapy, or even monoclonal antibodies alone. And I'm optimistic that this immunologic technique may give us a substantial fraction of patients who just need this 1 treatment and will stay in remission.

And it's available now. it was FDA approved earlier this year. We're using it off-study now in the in the clinic and getting very similar results. And there's a multitude of studies if you go into clinicaltrials.gov right now that are studying this in the upfront setting with chemotherapy [and] other immunomodulatory agents, so there's going to be more development. But I'm giving you the results for single agent mosunetuzumab.

PT Staff: Did findings from the follow-up study align with your expectations of the treatment’s performance?

Stephen Schuster, MD: Did I think this would happen? Yes. Why did I think it could happen? I think I think it was possible because I had previously done work with the CAR T cells in FL so I knew that these T-cell-based remissions (when that's the mechanism of action of your therapy) the remissions are quite adorable. So I have 10 year follow up on my FL patients that I treated with CAR T, investigational CAR Ts that we were making 10 years ago. So I know that these remissions can be really durable. And this is supporting that impression. The key is that you want to get it to a complete remission, the best outcome. And then the other thing is that we had a couple of patients who had recurrence [after] complete remission. [They] had recurrence of their lymphoma subsequently after a year or so, and they were retreated and achieve complete response again.

PT Staff: Mosunetuzumab is currently administered as a third line therapy treatment. Will it continue to be administered in this treatment sequence?

Stephen Schuster, MD: These therapies that work in these patients with a poor prognosis, they always work better when used earlier on in patients prior to multiple therapies. This is every drug that I've worked on the development of. So I anticipate that this drug will become part in some way, shape, or form part of our frontline therapy. I'm not saying we don't have a label for that now, I’m advocating that right now, and there are studies in progress— we'll have an answer in a few years. But I anticipate this will move up in therapy. And I'd love it as frontline therapy because it's chemotherapy free.

PT Staff: What are the adverse events to look out for when taking mosunetuzumab?

Stephen Schuster, MD: There are the 2 T-cell-based therapy-related adverse events (AEs) of cytokine release syndrome (CRS) and neurotoxicity. The neurotoxicity essentially (I think I'm not convinced we have it with the CD20 bispecific antibodies) but CRS is really what you need to watch out for. It usually happens during the first dose or the third dose of this medicine because we ramp it up during the first month. And there it's primarily fevers, low blood pressure. Very rarely do we have to use anti-cytokine therapies like tocilizumab (Actemra; Genentech, Inc.). [For] most patients, acetaminophen (Tylenol; Mallinckrodt Pharmaceuticals) or dexamethasone (Decadron; Hikma Pharma) maybe, is enough and it's generally self-limited. We grade it the same way we grade these toxicities for CAR T cells. The management for these AEs are pretty much spelled out in the package inserts in the medical literature for these products. It's very it's along the lines of the CAR T but you don't really get the severity.

PT Staff: Is there anything important that you would like to add?

Stephen Schuster, MD: I really insist that you get a biopsy; it could just be a needle biopsy even for flow cytometry to demonstrate that CD20 still exists on the surface of the tumor cells. In our original trial, which was a bunch of different B-cell lymphomas with this drug, what we found (retrospectively) is that little under 6% of the patients had no CD20 at the get-go, and if you don't see CD20, you don't respond. So either flow cytometry, or if they've had recent rituximab (Rituxan; Genentech, Biogen), you have to do a biopsy because the flow cytometric assay, the fluorochrome labeled antibody, can be blocked by rituximab and you won't see CD20.

If no recent rituximab, an FNA is fine with flow, but if recently toxin, [use] a CD20 stain just to catch that 5% to 6%.