Gilles A. Salles, MD, PhD: I would like to give you, today, my perspective as investigator of the L-MIND study regarding the recent approval of the combination of tafasitamab plus lenalidomide in patients with relapsed/refractory diffuse large B-cell lymphoma [DLBCL] that has been found to be transplant ineligible.
First, let me give you some background regarding this combination of tafasitamab and lenalidomide. Tafasitamab is a CD19-directed humanized monoclonal antibody that has been engineered in its Fc portion to improve ADCC, antibody-dependent cellular cytotoxicity, and ADCP [antibody-dependent cellular phagocytosis], phagocytosis activated by antibody. This modification of the Fc portion allows for greater cellular mobilization to kill the tumor cells.
Based on these mechanisms of action and the early results of tafasitamab as a single agent that had shown encouraging response rates, 20%, 25% in patients with relapsed/refractory lymphoma, it was logical to think about the combination with lenalidomide, which as we know, is a drug that can improve the cytotoxic activity of several immune cells, particularly NK [natural killer] cells. And it also has been shown when combined with rituximab to have an interesting and superior activity than rituximab alone in the setting of low-grade lymphoma.
The L-MIND study enrolled 80 patients with relapsed or refractory DLBCL who were treated with a combination of tafasitamab and lenalidomide. The initial first year treatment period was a combination of the 2 agents, which was followed, for the responding patients, by consolidation with tafasitamab alone until disease progression. During the first initial periods of the study, patients received weekly infusion of tafasitamab combined with lenalidomide, and then after 3 months, tafasitamab was delivered every 2 weeks.
The responses that were seen appeared rapidly, and the overall response rate that we published was 62%, and the FDA approval quoted the response rate in true DLBCL being 57%. We have seen that 37% of these patients with true DLBCL achieved a complete response. The other end point from the study was the progression-free survival, which reached 12 months in this transplant-ineligible population, and the duration of response.
When we look at the duration of response, while patients with a partial response unfortunately failed within a few months and progressed, patients with a complete response appeared to have a very durable complete response. In fact, the median duration of complete response had not been reached at the last follow-up. And what we have seen is that at 18 months, the majority of patients who have achieved a complete response have maintained the complete response, very encouraging results in this category of patients.
Safety wise, there have been adverse effects that we see with the use of lenalidomide, such as neutropenia, fatigue, some rashes linked to the disease, and eventually some GI [gastrointestinal] symptoms. The combination resulted probably in an increased number of neutropenia cases, and grade 3/4 neutropenia was observed in about half of the patients. However, when we looked at the number of patients with neutropenia per year, it was 1.1% neutropenic patient per year. So clearly stating that although we do see those, they are limited in numbers for our patients.
Furthermore, about 10% of the patients experienced infections in the study, showing that this is a rather safe combination even if we see this probably immune-based neutropenia. Thrombocytopenia occurred in about 20% of the patients, and overall there were no other major grade 3/4 adverse effects that were observed in this patient population, indicating that it’s a relatively easy to administer combination and rather safe with manageable adverse effects.
Transcript edited for clarity.