Patterns of Therapy Utilization in Relapsed/Refractory Diffuse Large B-Cell Lymphoma

Sean Patrick Bliven, MD, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, discusses results from a real-world study analyzing report patterns and therapy utilization in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), comparing overall survival among double-hit lymphoma (DHL) and non-DHL subgroups for chimeric antigen receptor T-cell therapy or autologous stem cell transplantation.

Transcript:

Hello. My name is Patrick Bliven and I am a physician doing internal medicine residency at the University of Alabama Birmingham, planning to go into hematology/oncology, and through that, have done a study in the O'Neal Comprehensive Cancer Center, looking at patients with double-hit lymphoma, a type of diffuse large B-cell lymphoma, to see kind of what the best treatment options and what the outcomes and kind of the order of treatments that they've been receiving has been.

So a little bit of background. The malignancy that we're talking about is diffuse large B-cell lymphoma. That is a pretty common non-Hodgkin's lymphoma where patients present with kind of a mass of lymphoma anywhere in the body and symptoms from that, being it's pushing on something, fevers, chills, things like that. And it's a type of cancer that actually is treated really well with first-line chemotherapy. Around 60-70% of patients are cured with that upfront chemotherapy, but we know that some patients do a little bit worse with treatments.

And one group of those patients are what we call patients with double-hit or triple-hit lymphoma. There are specific translocations of their cancer, whether they have what we call MYC and/or a BCL2 or BCL6 rearrangement, which is kind of hard to remember. So we call that double-hit lymphoma, and those patients we know do a bit worse. So what we wanted to look at was what type of treatments do these patients go through if they do not achieve a cure with conventional first time chemotherapy, or if they do, but then within a year, their cancer comes back. So with patients with double-hit lymphoma that have relapsed or refractory disease. And the standard of care for patients with the DLBCL that relapse is typically to go on to an autologous stem cell transplant.

So what we did is we took an electronic medical record database of around 7000 patients with DLBCL from all over the country, both academic centers and community centers, and we first wanted to map out what their treatment pattern was like. So we did that, and we found that there were around 6000 patients without double-hit lymphoma and around 367 patients that had double-hit lymphoma in our cohort. And we found that about 25% of the non-double-hit patients had relapsed or refractory disease, but 40% of patients with double-hit lymphoma went on to have refractory disease.

In order to get to that second-line treatment and autologous stem cell transplant, patients need to essentially be cured for a short time to get rid of all of their cancer. So we do that with very high doses of chemotherapy. We call that salvage intent chemotherapy, and we found that for patients without double-hit lymphoma, about 34% of them went on to that salvage intent chemotherapy to hopefully get a stem cell transplant. But almost 50%, 47% of the patients with double hit-lymphoma went on for that salvage intent chemotherapy.

However, a smaller proportion of the patients with double-hit lymphoma were actually able to move on to get the autologous stem cell transplant that was the goal of starting that second-line chemotherapy, whereas a larger percent, upwards of around 30% of patients, were able to do that with those that had non-double-hit lymphoma. So of the patients that got salvaging chemotherapy, a higher percent, around 35% without double-hit lymphoma, were able to move on autologous stem cell transplant, but only about 20% of the patients with double-hit lymphoma were able to move on to that.

And we then found that the outcomes overall were much worse for patients that underwent an autologous stem cell transplant if they had double-hit lymphoma compared to if they did not have double-hit lymphoma. And we know that in general, all patients with double hit-lymphoma do worse than those without double-hit lymphoma.

And the next thing that we wanted to do is we wanted to compare the outcomes for patients that underwent CAR T-cell therapy. CAR T-cell therapy is chimeric antigen receptor T-cell therapy, basically where we engineer a patient's T-cells to target their cancer. And that is a new therapy that is coming around for DLBCL. It has recently been studied in this relapsed and refractory setting, both as second-line treatment and as third-line treatment. Second-line treatment just started in the past few years. So we looked at it in the third-line setting, and we found that for patients that had double-hit lymphoma, if they had to go on to CAR T-cell therapy, since it was the third time we were trying therapy, overall, these patients did worse, but they actually did about the same as the patients that did not have double-hit lymphoma, whereas every other treatment we found that these patients do worse than those without double-hit lymphoma.

So that has, along with some new research that these CAR T-cell therapies can be used in earlier treatment settings, meaning that second-line setting, so for our patients that initially relapsed with disease, suggest to us that for patients that have double-hit lymphoma, instead of starting with that autologous stem cell transplant that is the standard of care for patients with relapsed or refractory DLBCL, moving on to a CAR T-cell treatment instead of an autologous stem cell transplant may be a better option for them, because more patients are able to go on to that with double-hit lymphoma and the patients actually do better with it.

So those are our overall findings. One, that patients that have relapsed and refractory double-hit lymphoma just in general are less likely to be able to proceed to an autologous stem cell transplant, 19% versus 32% of those without double-hit lymphoma, and that their overall survival is worse. Therefore, we suggest that it may be better to do CAR T-cell therapy in a relapsed or refractory setting for these patients.

I'd like to thank everyone for listening. I really appreciate it. We are very excited about our findings and are hopeful that they will continue to be used with a lot of upcoming clinical trials to guide therapy in the future.