Anti-CD19 Monoclonal Antibody Therapy in DLBCL

Nathan H. Fowler, MD:Tafasitamab is a new antibody that’s directed at CD19. It’s a monoclonal antibody, and it binds to the cell surface in B cells. The good thing is that CD19 is a pan-B cell marker, or it’s an antigen that is on almost all B cells, so it’s a great target for therapy for large cell lymphomas.

The L-MIND trial was recently presented, and this was a trial that combined tafasitamab with lenalidomide. Again, this is a monoclonal antibody, and they combined it with a drug that has been shown to change the microenvironment. It can potentially increase ADCC, and that’s antibody dependent cellular cytotoxicity. We’ve seen in other trials that when you combine lenalidomide with monoclonal antibody therapy, you get increased activation of certain benign cells within the tumor microenvironment that can potentially increase the activity of monoclonal antibodies. So the purpose of this trial was to combine a drug like this, lenalidomide, with this CD19 antibody, and hopefully increase the responses that we would expect from that antibody alone.

In the L-MIND trial, they looked specifically at patients with relapsed large cell lymphoma. This was a fairly beat up patient population. Many of these patients had 2 or 3 lines of prior therapy. Nearly all of these patients were transplant-ineligible. But despite that, they actually saw a very high overall response rate—58% overall response rate—and 33% of patients had a complete remission. At most recent follow-up, the average PFS [progression-free survival] in all patients in the trial was over a year. It was nearly a year-and-a-half, at 16 months.

In this trial, we also were looking at safety and tolerability of the combination. The good news is that the adverse effect profile really looked very similar to what we expect with lenalidomide as a single agent. That means that we occasionally see some neutropenia, rash, fatigue, and diarrhea, but not a lot of additional adverse effects with the addition of a monoclonal antibody to lenalidomide as a backbone.

With large cell lymphoma there are limited treatment options for patients, especially patients who are ineligible for transplant or have failed standard chemotherapy. In the past, we many times would give these patients chemotherapy again. Unfortunately many of them would not respond. So the nice thing about this nonchemotherapy-based regimen is we have another bullet in our gun that could potentially knock out large cell lymphoma. I think this regimen may eventually be combined with other therapies to hopefully achieve cures in many of these patients. But with an overall response rate of over 50%, and a duration of remission that’s over a year, it’s a great option for patients who really don’t have a lot of treatment options with available therapy.

Transcript edited for clarity.