Elizabeth Budde, MD, with Hematology & Hematopoietic Cell Transplantation at City of Hope talks about treating follicular lymphoma and Non-Hodgkin’s lymphoma.
Interview conducted by Ivanhoe Broadcast News in December 2023.
Can you tell me what follicular lymphoma is?
Budde: Follicular lymphoma is the most common indolent Non-Hodgkin’s lymphoma, and it typically inflicts patients in their ’60s and older. But we do see younger patients with a diagnosis of follicular lymphoma, too.
Did you treat Renee Bentson?
Budde: I did.
When Renee came in, what were her symptoms? What was she like?
Budde: When she came in, that was already after she had failed at least two or three prior anti lymphoma treatments using various regimens. She was quite frail due to the side effects from prior treatment. She has no symptoms, just from the lymphoma such as no fatigue, such as no difficulty with keeping up her energy level, and weight loss.
Is that very typical for these patients?
Budde: This could happen depending on the extent of the lymphoma involvement and also depends on the lymphoma’s behavior.
I think she told us she had been through four other clinical trials and the tumor would shrink, it would come back, but now she’s been able to be enrolled in a new clinical trial.
Budde: That’s correct.
Can you tell me a little bit about that?
Budde: Yeah. Renee was one of the first non-cohort patients who enrolled in this very new novel clinical trial and that was back in 2016, so it was a trial.
What is the name of that drug?
Budde: The name of the drug is mosunetuzumab. It’s a bispecific T-cell engager. So basically, before the invention of mosunetuzumab, all the antibodies for lymphomas were unique, specific, or what we call monoclonal antibodies. Basically, they only recognize one antigen or protein on the surface of a target. But for mosunetuzumab, which is a bispecific antibody, one arm recognizes a protein on the surface of the lymphoma cell, and the other arm recognizes a protein on the surface of our immune T-cells. What it does is it grabs the T-cells and redirects the T-cells to the neighborhood of the lymphoma cells. Now, by grabbing this protein on the lymphoma cells, so would you allow it?
Is it targeting your body to fight itself directly into the lymphoma?
Budde: Exactly. It’s like providing a pair of special glasses for your immune T-cells so now they’re able to see the target, direct them to the target. The T-cells are activated, and they kill up the targets as directed.
How is this drug delivered?
Budde: The drug is delivered intravenously. For the first cycles, it’s given in a step-of-dosing fashion to minimize the potential side effects so allows us to escalate to the photos. Once the photos are reached, starting from cycle two and on, it’s only one dose every three weeks, convenient. It’s outpatient delivery.
One dose every three weeks after how long?
Budde: For a patient who achieved complete remission, it’s only eight cycles. For those who are nine in remission, it’s up to 17 cycles. It’s what we call no-fixed dosing duration.
Now, I don’t remember this correctly. I think Renee said that, maybe after four cycles, she was getting no lymphoma detected in her body.
Budde: In her case, no. After two cycles, and six weeks, she achieved complete remission. But we want the remission to be durable. Complete remission does not mean no detecting of lymphoma. Complete remission is based on the result of the PET scan, which has its limitations. For a patient who achieved complete remission, it’s eight cycles.
Now this clinical trial, do you remember some specific results from it?
Budde: I do. Renee joined in the very beginning part of the clinical trial and subsequently, we learned so much from patients like Renee and we were able to find a dose that works for most patients. There is a pivotal clinical trial. All patients in the pivotal cohort received the same dosing regimen, one milligram first week, two milligrams, and then 60 milligrams as the highest dose. Subsequently, it’s 30 milligrams each cycle. In this study, with 90 patients treated the same way getting intravenous dosing being managed in the outpatient setting, the overall response rate is 80 percent meaning 80 percent of patients have responded to the treatment and 60% of the patients are in complete remission. It is a very clean PET scan.
Have you seen anything work as well as this?
Budde: Not so much. We have seen CAR T-cells also given to patients with real refractory follicular lymphoma, but we’re comparing different patient populations. Mosunetuzumab is an off-the-shelf product and CAR T-cells require manufacturing so two different immunotherapy, I would say, efficacy-wise, are pretty similar given the difficulty to treat for these kinds of patients.
Now, there’s no cure for lymphoma, right? Is that the closest thing you’re going to get?
Budde: Yes. All the conventional therapy for follicular lymphoma doesn’t result in a cure. But for this novel immunotherapy, we don’t know. Patients like Renee who has been in remission since now 2017. Is she cured? I hope so. But we just continue to follow her and other patients in the longer term.
I feel like we can’t throw around the term “cured” at all. But I feel like, whenever you can say, “this is the closest thing or close or possible,” that just comes around so infrequently in diseases like this.
Budde: Exactly. We’re pretty excited. Now we were following those patients on this pivotal cohort, those patients who are treated after Renee, two years out, more than half a patient still in remission so it’s very promising.
Very promising because Renee, she’s a very hopeful person. But she was a little worried that there was going to be nothing that could stop it.
Budde: Yeah. But I think now she’s in very durable remission, so we’re pretty excited for her.
Now, is there anyone with follicular lymphoma that would not be a good candidate for this drug?
Budde: The only patient that I think would not be a candidate would be if they don’t have the target which is the very common antigen protein expressed on the follicular lymphoma cells. If they have targets, they could be a candidate, but if they don’t have the target then this would not be the right treatment. Nowadays, there are similar treatments targeting a different protein. It’s available in clinical trials.
END OF INTERVIEW
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