Moving Towards Immunotherapy for Newly Diagnosed DLBCL Patients | Paolo Strati, MD | ASH 2023

Hello, everybody. My name is Paolo Strati. I'm a physician and assistant professor in the Department of Lymphoma and Myeloma at MD Anderson Cancer Center in Houston, Texas. During this ASH, I will be presenting results from an investigator-initiated clinical trial where we combine acala-brutinib, which is an agent able to target the B-cell receptor in large B-cell lymphoma to immunotherapy with lenalidomide-arytaxin in patients with previously untreated but advanced stage and high tumor-barten follicle lymphoma. Follicle lymphoma is a slow-growing B-cell non-Hodgkin lymphoma. It's actually the most common slow-growing or intolerant B-cell lymphoma in the United States and Europe. And it's currently treated the first time with chemotherapy. So there's been a lot of interest to trying to develop instead chemotherapy-free approaches for this patient population, particularly because patients with follicle lymphoma tend to be older and frail, and many times they're not able to well tolerate chemotherapy. The standard immunotherapy for patients with follicle lymphoma is currently represented by the combination of lenalidomide-arytaxin, also called R-square, but is not formally approved by the FDA or the EMA in Europe as a first treatment for follicle lymphoma. And that's because it's not superior to chemotherapy for this patient population. So in this trial, based on some experiments that we performed in the lab, we have decided to add to R-square acalabrutinib, which is a pill currently approved by the FDA for several types of B-cell lymphoma, but not for follicle lymphoma. And the rationale is that in the lab we saw that it may make immunotherapy stronger by targeting a very specific type of immune cell called monocyte or macrophage. This was a phase two trial. We enrolled overall 24 patients with previously untreated advanced stage and high tumor burden, so really bulky follicle lymphoma. Overall, the combination was very safe. It didn't seem to bring any additional toxicity as compared to R-square alone or acalabrutinib alone, but most importantly, was very effective. Typically, with R-square alone, only 50% of patients achieve a complete response. In this trial, overall 92% of patients were able to achieve a complete response. We also collected peripheral blood from these patients and we performed some experiments and we were able to observe that acalabrutinib, as we expected, was able to change the monocytes and macrophages in these patients and make them more anti-tumoral, so better at attacking the lymphoma synergistically with immunotherapy. So overall, we're very excited about these results. Because of these results, we have amended the trial. We are allowing 26 more patients overall. This will be a 50-patient trial. And because the responses were achieved very early, we have decreased the number of cycles from 13 to 6 cycles. And if the larger trial will hold true, hopefully we'll move to the next step. There will be a randomized trial comparing this new immunotherapy to chemotherapy. And hopefully, on the long term, we will be able to bring to FDA and EMA approval of immunotherapy as a first treatment for fully grown lymphoma.