Academic Focus: CAR-T Therapy for Relapsed/Refractory NHL - Episode 2

Unmet Needs in Treating Relapsed NHL


Matthew Lunning, DO: It depends upon what population you’re talk about. I go back to the data that we know from the SCHOLAR-1 study, which looked at patients who were refractory to their frontline therapy or refractory to second-line therapy, or those who had recurred within 12 months of an autologous stem-cell transplant. This was a large study looking at the relapsed/refractory diffuse large B-cell lymphoma population, which was very sobering.

There were 636 patients involved in this study taken from clinical trials as well as retrospective cohorts. Within these populations, which are pretty high-risk large-cell lymphoma populations, we were looking at therapies that had an overall response rate around 20%, complete remission rates less than 10%, and median overall survival around 6 months, all of which indicates that this is an unmet need.

If you have to stare a patient in the eyes and tell them: “In 2 years only 1 out of 5 patients are alive that were in that study,” that’s a big deal. We’re really striving to improve therapies in that patient population, as well as in relapsed/refractory large-cell lymphoma in general.

In the heavily pretreated diffuse large B-cell lymphoma population, I would consider somebody that has received font- and secondline therapy, especially if they were able to receive an autologous stem-cell transplant and their lymphoma has relapsed—namely their diffuse large B-cell lymphoma since retrogrades can occur post-transplant or in the relapsed setting. You want to be mindful that you have a biopsy that shows diffuse large B-cell lymphoma because, if it doesn’t, your treatment paradigm may change and your options in that setting may differ.

But in that heavily pretreated diffuse large B-cell lymphoma population, we’re living in a lot of single-arm phase II studies, which have accrued 20 to 30 patients—really demonstrating overall response rates which are best in the living 20% to 30% range. Even with that there appeared to be very little durability with those responses. We are looking for better therapies in the relapsed/refractory diffuse large B-cell lymphoma spectrum.

Now to digress briefly into a discussion on “common controls,” which can be used in a randomized fashion in the relapsed/refractory large-cell lymphoma study, I’d like to mention a study that was presented at ASH [American Society of Hematology] in 2017 by Dr Laurie Sehn ,MD, and colleagues, looking at the control arm, which was bendamustine and rituximab, in patients who had relapsed/refractory diffuse large B-cell lymphoma and gave them a common regimen, which I use in my practice. The results were quite sobering in the diffuse large B-cell lymphoma relapsed/refractory setting, with 20% overall response rate and a median overall survival of 4.7 months in the control arm.

Many patients couldn’t even get through several months of therapy either because of the toxicity or their disease continued to progress through chemotherapy, which is common in the compendium listing for use in relapsed/refractory diffuse large B-cell lymphoma. Now there are others; there’s data that show that ibrutinib or lenalidomide may derive benefit. I have used those in the relapsed/refractory diffuse large B-cell lymphoma setting.

Transcript Edited for Clarity