L-MIND Trial in Relapsed/Refractory DLBCL

Transcript:

Andre Goy, MD, MS: We talked quite a bit about CAR [chimeric antigen receptor] T-cell therapy and some immunotherapy. But to wrap up our session, we are going to talk a little bit more about how there are a lot of novel options. There are over 2000 new drugs in the pipeline of lymphoma, so we have a lot of work in front of us. Please enroll and refer patients for clinical trial. I think this is really important. But we talked about antibody drug conjugates. One of them that is approved is brentuximab vedotin in CD30-positive disease, but also obviously in T-cell and Hodgkin lymphoma. In large cell lymphoma, they are trying to take advantage in a frontline setting in combination with R-CHOP [rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone]. Grzeg, do you want to mention? What do you think about the combination of brentuximab vedotin: BV-CHP [brentuximab vedotin, cyclophosphamide, doxorubicin, vincristine, prednisone]?

Grzegorz S. Nowakowski, MD: The initial results from brentuximab vedotin, cyclophosphamide, doxorubicin, vincristine, prednisone actually looked quite intriguing in patients with CD30-positive DLBCL [diffuse large B-cell lymphoma]. I think this was not a controlled study, it was just a phase II study, so we’ll have to see if those results are maintained in the additional studies in this setting. But it’s a very novel way of approaching it.

Andre Goy, MD, MS: Kami, you want to talk about tafasitamab as a single agent but also in combination, the L-MIND trial?

Kami Maddocks, MD: Yes, the L-MIND trial with tafasitamab is an Fc-enhanced CD19 antibody that was evaluated in a phase I trial in all non-Hodgkin lymphoma. Interestingly there were a few complete responses, complete remissions in diffuse large B-cell lymphoma, which you don’t typically see with antibody therapy alone. Based on that, the L-MIND trial was designed, and this was a phase II single arm study looking at the MOR208, tafasitamab, CD19 antibody in combination with lenalidomide. The combination was given for 1 year, and lenalidomide was given at a dose of 25 mg daily. For patients who completed 12 months of therapy, they were allowed to continue on the antibody if they had stable disease or better.

The results were actually very promising. The overall response rate in these 80 patients was 60%, with a 42% complete remission rate. The median duration of response of 22 months. I think the combination was very well tolerated. About 50% of patients had dose reductions in the lenalidomide, but 70% of them maintained at a dose of 20 mg or higher. What we saw from the toxicity was primarily what you see with lenalidomide alone. Once the lenalidomide was stopped at 12 months, the toxicity significantly dropped, and the antibody was just given alone. Responses were similar across all cohorts. There was a little bit better overall response in patients with lower IPI [International Prognostic Index scores], only 1 prior therapy. This was done in a transplant-ineligible population and in a non-GC [non-germinal center subtype] compared to the GC subtype, but the GC subtype still had a 50% overall response rate.

Andre Goy, MD, MS: The L-MIND trial was impressive in the response rate and durability. Do you think that this is something that might interfere in response to CAR T anti-CD19 for the therapy?

Kami Maddocks, MD: That a great question. When you have the same target with CAR T and it’s been so beneficial and then you’re looking at a CD19 antibody, we don’t have great data. I think we’ll need to have more. There is an abstract from ASH [the American Society of Hematology 2019 annual meeting], a preclinical abstract, that shows that CAR T is still effective in cells that have been treated with tafasitamab. There are a few patients who were treated on trial who went on to get CAR T and have done well on that therapy. But certainly, using it either before or even after the CAR T is something that we’ll have to have more patients treated with to understand that.

Andre Goy, MD, MS: If you can remind our audience, the L-MIND trial had patients who were rituximab refractory.

Kami Maddocks, MD: About half the patients were rituximab refractory.

Andre Goy, MD, MS: The activity was still impressive in patients who were rituximab refractory.

Kami Maddocks, MD: Correct.

Andre Goy, MD, MS: It’s not the same target, but just to make sure patients respond and benefit.

Nathan H. Fowler, MD: The antibody CD19, it’s a monoclonal. Other than infusion reactions, we haven’t seen a lot of adverse events with the drug. In fact, the adverse event rate looks very similar to what you see with something like R-squared [rituximab, lenalidomide] in the same population. I think CAR T-cells are still a spicy meatball. There are some patients who I would not be too comfortable giving CAR T therapy, especially patients with some type of organ dysfunction. That would be a very nice population that you would still want to consider something like this for.

Andre Goy, MD, MS: True. Some of these patients have very durable responses to the combination. Only R-squared ....we have a patient at least over 3 years in relapsed large cell lymphoma, she had a double expressor, and she has done very well.

Kami Maddocks, MD: I think we’re all at centers that can do CAR T, so I think we have a little bit of a bias toward that. But I think if you look at the general US population, you have to be able to get to a referral center. You have to be able to travel back and forth. You have to probably spend time in a major city. But the reality is for insurance approval and all that, is it’s not that easy for everybody to have access to that. This regimen would be something that would be easy access for any patient with relapsed large cell lymphoma.

Grzegorz S. Nowakowski, MD: In any phase II study you always worry about patient selection and if those results are actually reproducible and if they can be compared with other populations. So here the investigators also conducted a study where they look at the single agent, lenalidomide. They took real-world data of over 400 patients, and they matched them on the patient level to the characteristics of patients on the clinical trial, a very tight match. I haven’t seen the actual results of the study, but from the press release we know that this match was actually quite successful. Indeed in the same population of patients, lenalidomide just did what we typically would expect, with a response rate approaching 40% and a relatively short duration of response. This doublet appears to be doubling response and significant...of response.

Transcript Edited for Clarity