Tafasitamab plus Lenalidomide as a Treatment in Patients With R/R DLBCL


Oncologists discuss the efficacy and safety of a tafasitamab plus lenalidomide for relapsed/refractory DLBCL and share personal experiences relevant to its use.

Matthew Lunning, DO, FACP: In those patients who can’t go to CAR [chimeric antigen receptor] T-cell therapy and aren’t transplant eligible, but [where] it’s second line, I like tafasitamab and lenalidomide because often if they’re chemo-refractory, that’s the fastball; I want to throw them a curve ball. A CD19 monoclonal antibody plus an IMiD [immunomodulatory imide drug], like lenalidomide, is an attractive option.

If you look at the L-MIND data, there were some interesting pieces that people should know about. One of them is 1 to 3 prior lines of therapy; initially, patients with primary refractory disease weren’t allowed. The double-hits and triple-hits; we’ve discussed before that there were some sprinkled in there. They looked at those with a creatinine clearance greater than 60 mL/min and performance status. I’m not afraid to give lenalidomide to a patient who has a creatinine clearance of 40 mL/min. I just need to dose adjust the lenalidomide appropriately.

Tafasitamab is negligible. It’s an active agent that’s front-loaded, so it has the opportunity in aggressive disease to capture response and potentially have durability if you can get them into a CR [complete response], and I think that’s what the data support. There are a multitude of other agents that I think are going into retirement, including single-agent ibrutinib. I think R2 [rituximab, lenalidomide] is probably in retirement. Pola-BR [polatuzumab vedotin, bendamustine, rituximab]: the smartest thing that the NCCN [National Comprehensive Cancer Network] guidelines did was polatuzumab plus or minus rituximab plus or minus bendamustine. Gone are the days of giving a milligram of bendamustine so that you can give polatuzumab-rituximab. But if POLARIX hits and we all switch our practice, then what’s going to fill the space of polatuzumab? Bispecifics are on their way. I’ll stop there.

Grzegorz S. Nowakowski, MD: Caron, Matt mentioned the tafasitamab and lenalidomide combination. What’s your experience with this combination? What’s your take on its efficacy and potential toxicity?

Caron Jacobson, MD: We’re using it largely in patients who have gone to CAR T-cell therapy and subsequently relapsed. Often, we like to rebiopsy them and confirm that they’re CD19 positive, which many are at the time of relapse. Sometimes it’s used for patients who are not CAR T-cell candidates or autologous stem cell transplant candidates. As Matt said, it’s one of his preferred regimens for those patients. The points that Matt made are valid; that some of the patients who went on that study are some of your healthier patients with relapsing large B-cell lymphoma with a better prognosis. When we’re using it for CAR relapses that are often double- and triple-hit lymphomas, I don’t think we’re necessarily seeing the same responses. But we’re definitely still seeing responses in the clinic.

Other than the adverse effects of the lenalidomide, which you can dose adjust in order to overcome, the regimen is pretty well tolerated. I’m glad it’s in our armamentarium, but it’s a little challenging to understand how to sequence it at this point, given that I believe CAR T-cell therapy cures people with diffuse large B-cell lymphoma and I don’t want to jeopardize that, and we don’t know how it affects sensitivity to CAR if you use it before CAR T-cell therapy.

Leo Gordon, MD: To follow-up on a couple of things Matt and Caron said, I fully agree that referral shouldn’t be for modality. Referral should be for an opinion about management of lymphoma and then the modality gets placed in its appropriate position. If you look at the people who have relapsed within a year or have primary refractory disease—Fred can speak to this—based on the data from ZUMA-7 and TRANSFORM, in at least those 2 studies, it looks like CAR T-cell therapy offers a better progression-free survival and better response rate than autologous stem cell transplant.

That said, there are probably some patients whom you might still consider giving a transplant. For example, if you expect a patient with early-stage disease to be in CR at the end of treatment, you give 6 cycles, and there’s still a small residual mass in the axilla and nothing else. Those are patients who might be OK with radiation and maybe an autologous stem cell transplant. Maybe they’d be OK with only radiation. There are some patients whom I’d still think about giving an autologous transplant. I have the same criteria for transplant as Matt does, and we like to see people in CR or near CR. When we were looking at ZUMA-7, that was a concern of mine, because all people needed was a PR [partial response], which to me isn’t enough to go to transplant. But as it turned out, only 30% of people in ZUMA-7 wound up going to transplant, and you can speak to this.

The comment about tafasitamab and the clinical trial and picking the best patients is true, but I’m afraid that applies to many clinical trials that we do. Are we really doing clinical trials in patients who we see every day? Or are we doing clinical trials in a subset of robots? The way we do clinical trials and the way the FDA [United States Food and Drug Administration] requires us to do clinical trials has always been concern of mine. That’s why some of the real-world data are important to look at.

Grzegorz S. Nowakowski, MD: You touched on something very important. Real-world data can inform some of those treatment decisions and compare the patients. It’s always difficult to make intra-trial comparisons and conclude which regimens are better, because the inclusion criteria have risk factors that vary quite a bit in those studies.

Transcript edited for clarity.

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