Recent Updates on Management of Diffuse Large B-Cell Lymphoma - Episode 9

Newer Approvals for Previously Treated DLBCL

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A panel of experts review the FDA approvals of loncastuximab tesirine and selinexor for the treatment of DLBCL in patients who have received at least 2 prior therapies.

John Leonard, MD: We’ll now move on to the multiply relapsed setting, and the “third-line and beyond,” which beyond is hopefully a pretty good beyond, not a black hole of treatments. I have to say that this area has become very exciting and promising, between CAR [chimeric antigen receptor] T cells, and we have multiple that we’ll talk about. We’ve got a couple of other agents that we’ll get to in a minute, and there are a lot of exciting agents in clinical trials, that are, I think in some cases, beyond the marginally active in a subset of patients with select large cell lymphomas, but potentially agents that could make a difference in the third-line setting, and perhaps even sooner. Cyrus, I want to ask you about the drug that was approved recently, loncastuximab tesirine, or lonca. This is another antibody-drug conjugate approved for patients with multiply relapsed diffuse large B-cell lymphoma. Tell us a little about your take on the data with this agent in this setting.

Cyrus Khan, MD: Sure. They’re great additions. Loncastuximab is an antibody-drug conjugate that conjugates an anti-CD19 monoclonal antibody to a pyrrolo diazepine alkylating agent by a stable link…one of the other ADCs now. It was approved recently, based on the LOTIS-2 trial, which was by Paolo Caimi, MD, and associates, and this is in patients with 2 lines of therapy, so was approved in the third line of therapy, and it took all comers. There were relapsed/refractory patients, there were patients with double or triple hit lymphoma, you also had patients with transformed follicular lymphoma in this setting. Interestingly, when you look into it, there are patients who received transplants, obviously, but also, post–CAR T-cell therapy. Not only that, patients who responded, some of them went on to receive an autologous transplant, or later on, get CAR-T cell therapy also. So we saw all kinds of different patients. This was single agent, it’s given every 3 weeks, and treatment was continued until progression or toxicity. When you look at the studies, the response rates are approaching 50%, CRs [complete responses] are almost 25% in this difficult-to-treat population. Duration of response was about a year or so, 12 to 13 months, depending on what subset of patients you’re looking at. Looking at even the double or triple hit, there were impressive results even in those. You’re approaching CRs even in those types of patients, so I think it’s a very important addition to our armamentarium of treating these types of patients. As far as toxicity’s concerned, it’s generally well tolerated. One of the unique things we see is fluid retention or edema, and that is why dexamethasone is used, starting 3 days prior to the infusion. We had an expanded access protocol open in our center about 8 months prior to the approval, so we were able to treat a number of patients, even patients who were post-CAR T, on this. Even anecdotally, I have seen quite a good response, and I’m sure everybody has had similar responses.

John Leonard, MD: Have you had any experience with this agent, Greg? What’s your take on the data?

Greg Nowakowski, MD: I don’t have any personal experience with the agent, we are just getting it to the pharmacy after approval, but the data look very promising. The study was one of the largest ones in the relapsed/refractory setting, and it captured quite a few patients with post–ؘCAR T-cell relapse as well, showing a promising activity in this space. It’s an additional bullet for our armory.

John Leonard, MD: Loretta, another drug that’s been approved in this setting has been selinexor, a different sort of drug in that it’s an oral agent, and we’ve been involved in some of the trials here. What’s your take on selinexor and how it works, and when you might use it based on the data that we have available?

Loretta Nastoupil, MD: Sure. Selinexor is an oral nuclear export inhibitor. It’s kind of surprising to me that it got approved in large cell lymphoma, because I had sort of lost sight of it. It’s approved in multiple myeloma, so I think this is one drug where the community oncologists may have more experience with this than I do, for instance. And as you highlighted, it’s an oral therapy. The overall response rate was about 28%, so it wasn’t particularly impressive, but what was interesting is that about 12% of patients had a CR, and that CR was quite durable. So this is an option for those patients who I feel have probably exhausted some of the more potentially exciting therapies, who maybe have lost CD19, for instance. They may not be appropriate yet for hospice but need an oral therapy that can be taken closer to home, and not be confined to an academic center like ours. That’s where I do see this being a potential therapy.