Odronextamab Demonstrates Efficacy, Safety for Heavily Pretreated Patients With DLBCL Progressing After CAR T-Cell Therapy

Results from the ELM-1 Study

Matthew Matasar, MD, Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey, presents insights into the ELM-1 study, in which odronextamab monotherapy demonstrated encouraging antitumor activity, and a manageable safety profile among the difficult-to-treat population of heavily pretreated patients with diffuse large B-cell lymphoma (DLBCL) who progressed after CAR T-cell therapy.

These results were presented at the 2024 European Hematology Association (EHA) Congress in Madrid, Spain.

“These data support the potential role of odronextamab in the treatment paradigm for R/R DLBCL,” Matasar and colleagues wrote. “Further studies to help inform the optimal sequencing and combinations of odronextamab with CAR-T therapy are warranted.”

Transcript:

Hi, I'm Dr Matt Matasar. I'm the Chief of Blood Disorders at the Rutgers Cancer Institute. On behalf of my coauthors and coinvestigators, it's my pleasure to discuss with you today our updated results of a study we presented at EHA this year, evaluating the activity and safety of odronextamab in patients with diffuse large B-cell lymphoma who have progressed subsequent to CAR T-cell therapy. And this is a cohort analysis derived from our ELM-1 study.

As I'm sure you are all aware, odronextamab is a CD20-CD3 bispecific antibody that has been evaluated in a number of histologies, including relapsed/refractory diffuse large B-cell lymphoma. We know that CAR T-cell therapy remains an important treatment in patients with relapsed/refractory large B-cell lymphoma, but standard of care for patients who have progressed through or following CAR T-cell therapy remains unclear. The study gives us an opportunity to evaluate the activity and safety of odronextamab in this challenging clinical scenario.

Indeed, in the ELM-1 study, we had 44 patients who were treated on protocol who had had prior CAR T-cell therapy, allowing us to better evaluate this specific clinical scenario. The patients in ELM-1 who were post-CAR really did not differ meaningfully in terms of their characteristics vs those who were CAR-naive in terms of median age, prior lines of therapy, IPI, bulk, histologic subtype, refractory nature of disease, and so on.

But despite the fact that patients had progressed following or immediately after CAR T-cell therapy, we saw that odronextamab was just as active as it was in CAR-naive patients. This is a relatively short follow-up, with the median duration of follow-up of only 5 months. But that being said, the overall response rate in post-CAR-T patients was 48%. And indeed, some of these responses are quite durable.

The median PFS in our post-CAR patient population was a 12-month median PFS of 33% and a 12-month OS rate of almost 50%. In terms of durability of response, both duration of response and duration of complete response have not yet been reached. Admittedly with still relatively short follow-up, but it really is an encouraging sign that responses in this context may have some durability to them, and we'll certainly be watching this data mature over time.

Perhaps equally important is an evaluation of the safety of bispecific antibodies in this context. Encouragingly we saw no new safety signals, when you're comparing the rate and severity of treatment-emergent adverse events in patients who had had prior CAR vs those who were CAR-T naive. This includes CRS, neurotoxicity, and mild suppression as well. Interestingly, we see that patients who were patients who were post-CAR-T, their baseline immunologic characteristics did have lower CD4, CD8 T-cell counts. That's not surprising, I'm sure.

But despite this difference in baseline T-cell quantity, we still saw significant T-cell expansion following treatment with odronextamab. This occurred very reliably by cycle 5 to 8 as we reported in the poster. So what do we learn from this subset of now? For now, we learn that bispecific antibodies can be both a safe and active approach in patients who have been failed by CAR T-cell therapy, here specifically with odronextamab.

We continue to want to watch these data for the durability of response, but it's encouraging that the activity is high and so far responses have been durable at an early follow-up time point. Again, my name is Matt Matasar, and on behalf of my fellow ELM-1 investigators, thank you for your interest.

Source:

Michot JM, Matasar M, Harrison C, Crombie J, et al. Odrononextamab demonstrates durable complete responses in patients with diffuse large B-cell lymphoma (DLBCL) progressing after CAR-T therapy: outcomes from the ELM-1 study. Presented at the European Hematology Association 2024 Congress June 13-June 16, 2024. Madrid, Spain. Abstract P1162