Novel Therapies for R/R DLBCL

Ian W. Flinn, MD, PhD: John, I want to go back to you and talk about some of the other therapies that have recently been approved for relapsed large B-cell lymphoma. First, let’s talk about polatuzumab. Polatuzumab was approved in combination with bendamustine-rituximab. What has your experience been here, and how are your using this regimen?

John M. Burke, MD: Just to summarize, polatuzumab is an anti-CD79b antibody-drug conjugate linked to MMAE [monomethyl auristatin E], the same drug that’s in brentuximab vedotin. Data supporting its use comes from a randomized phase 2 trial, a relatively small trial of 80 patients, where the addition of polatuzumab to bendamustine and rituximab improved many efficacy outcomes, including complete response rates, progression-free survival, and overall survival. To my knowledge, this is still, since the PARMA study decades ago, the only randomized trial in relapsed large B-cell lymphoma that demonstrates a survival advantage with 1 regimen over another. This was a pretty significant leap forward.

Even bendamustine-rituximab can lead to considerable toxicities in these patients. The polatuzumab–BR [bendamustine-rituximab] combination can cause neutropenia, and polatuzumab is also associated with peripheral neuropathy. 

I have found this to be a useful regimen for a similar patient population relapsing after an autotransplant. I even used it before CAR [chimeric antigen receptor] T-cell therapy was around. And I’ve used it as a second-line therapy in patients not eligible. 

Just to elaborate on that, the FDA approval for this combination is for treatment in the third-line setting or beyond. But the study included second-line patients. In fact, those patients, in a subset analysis, had better outcomes. I’ve used it as either second- or third-line therapy. I have not had any trouble getting it covered by insurance, even in the second-line setting. That’s where I’ve used it.

Ian W. Flinn, MD, PhD: Thanks. You talked about using this prior to the introduction of CAR T cells. It’s attractive as a bridging therapy for patients who require it, that were acquired CAR T cells. But I certainly worry about a T-cell–depleting agent like that and giving it prior to acquiring the leukapheresis product. It’s an important new therapy for patients. I’ve been very impressed with its efficacy.

Kami, what about the selinexor? This is an oral agent, and it’s attractive because of that. How are you using that in your practice?

Kami J. Maddocks, MD: I’ll be honest, I have not used this in my practice. Where I see a role for this is based on it being an oral therapy. In regard to toxicities, we see cytopenia, some GI [gastrointestinal] toxicity, fatigue. It does require some work, as far as the premedications you use. However, it seems tolerable with those premedications. To me this is something that if you have a patient who relapses after CAR T-cell therapy, isn’t eligible for a trial, wants to try something, or maybe if you have an older patient who is not eligible for transplant, is not eligible for CAR T, and wants to try something, it’s an oral therapy. As I said, it has toxicity, but that can be managed. That’s really where I see it being used. I have not personally used it.

Ian W. Flinn, MD, PhD: You’re not using it in the second-line setting mostly because the results weren’t as impressive as the results with BR [bendamustine-rituximab]–polatuzumab or other agents, I assume. Is that right?

Kami J. Maddocks, MD: Yeah. I would say that in the second-line setting, for somebody who’s not going to be eligible for a curative therapy, I’m using tafasitamab-lenalidomide; or prior to that, if I could get access to it, as John said, BR [bendamustine-rituximab]–polatuzumab.

John M. Burke, MD: I was just going to add 1 thing, Ian. The trial with selinexor required at least 2 prior lines of therapy. It hasn’t been well studied as a second-line therapy. As was pointed out, the responses are probably less impressive than what we’ve seen with some of the other drugs that we’re mentioning that have become available in the last couple of years for relapsed disease. Moving forward, selinexor may potentially be combinable with chemotherapy or other drugs. That may really be the future of this drug—to combine it with some of the other therapies that are out there to see if they can improve efficacy. There is personal hope for this drug, in regard to having more utility.

Amitkumar Mehta, MD: One more thing on that. There were a few case reports of CNS [central nervous system] penetration with selinexor. I’ve seen responses in CNS involvement. There are also studies ongoing. So that’s an extra niche for this drug.

Ian W. Flinn, MD, PhD: Great, we’ll look forward to the results of that trial that you mentioned.

Transcript Edited for Clarity