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Investigating Odronextamab for R/R FL and DLBCL in the ELM-2 Study With Sabarish Ayyappan, MD

At the 2023 American Society of Hematology (ASH) Annual Meeting, Oncology Data Advisor sat down with Sabarish Ayyappan, MD, the Director of Hematological Malignancies at the City of Hope Cancer Center, to discuss the ELM-2 study which investigated odronextamab for relapsed/refractory (R/R) follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL).  

Oncology Data Advisor: Welcome to Oncology Data Advisor, I'm Keira Smith, and today we're recording here at the ASH Annual Meeting. I'm joined by Dr. Sabarish Ayyappan. Thanks so much for coming on today.

Sabarish Ayyappan, MD: Thank you, Keira. I'm Sabarish Ayyappan. I'm the Director of Hematological Malignancies at the City of Hope Cancer Center in Atlanta, and an Associate Professor of Medicine as well in the City of Hope Cancer Center.

Oncology Data Advisor: Awesome. Happy to speak with you. Today, we're talking about your presentation on the final analysis of the phase 2 ELM-2 study of odronextamab in patients with relapsed/refractory diffuse large B-cell lymphoma. For background, would you like to tell us a little bit about odronextamab, its mechanism of action, and how it's been used in hematology so far?

Dr. Ayyappan: As you know, diffuse large B-cell lymphoma is a potentially curable cancer, but about 40% of patients could relapse, and we have chimeric antigen receptor (CAR) T-cell therapies that have been approved for treatment of refractory diffuse large B-cell lymphoma. But a lot of patients could still relapse or do not respond to CAR T-cell therapy, and there's an unmet need for newer treatments for this disease.

In that space, we have the novel class of drugs called bispecific antibodies that bind to the T-cell and the CD3 and the cancer cell and the CD20. Odronextamab is a human IgG4 bispecific antibody that binds to CD3 and CD20, and it has shown in preclinical models to be effective in lymphoma. And we have some preliminary data from the ELM-1 study where patients post–CAR T were treated with odronextamab and had good responses. We also had some interim data on the efficacy of the odronextamab in the phase 2 ELM-2 study.

Oncology Data Advisor: Awesome. What did the ELM-2 study investigate and what results did you find?

Dr. Ayyappan: So, the ELM-2 study was a phase 2 study that enrolled patients with relapsed and refractory non-Hodgkin's lymphoma, of which relapsed and refractory diffuse large B-cell lymphoma was a cohort. It included patients who are refractory to treatment with more than two lines of therapy, including an anti-CD20 antibody and alkylator. The study was open in 14 countries and enrolled patients from March 2020 to May 2022. We presented the data on the efficacy and the safety in 127 patients during this ASH Meeting.

The baseline characteristics of these patients were having some high-risk features, including the double-hit and the transformed lymphomas. There were also some older patients, aged greater than 75 years, on the study.

To mitigate the side effect called cytokine release syndrome, there was a step-up dosing for the odronextamab, and initially it was a 1 mg/20 mg dosing. However, to reduce the rates of cytokine release syndrome, there was an extra step added and it was at 0.7 mg, followed by the 4 mg, then a 20 mg dose, finally achieving the intended dose of 160 mg. That way, we were able to reduce the side effects of cytokine release syndrome when the patients were getting started with treatment.

As far as looking at the data that we presented today and looking at the efficacy of the drug, the overall response rate was about 51%, including 32% of patients who had complete response. And the other exciting thing from the efficacy that we had seen was that most of the responses were durable with a duration of complete response up to 18 months. When you look at the 24-month complete response rate, it was at 47.2%. And in patients with difficult-to-treat options, this is very exciting news that we have a medication that could work and is durable in its responses.

Oncology Data Advisor: Absolutely, it's very exciting. So, what are the next steps for odronextamab?

Dr. Ayyappan: In terms of the next steps, there are all the clinical trials underway where we are bringing the odronextamab in earlier lines of therapy, because this was initially studied only in patients in the relapsed and refractory setting. We think the T-cell fitness may be of importance. To improve on the efficacy, this is going to be studied in earlier lines of treatment, in combination with chemotherapy, and also in the relapsed and refractory setting in combination with other efficacious agents. But the combination could add to the efficacy and possibly help all these patients.

Oncology Data Advisor: Awesome. Well, thank you so much for talking about this research today. It was wonderful to hear about the trial. We look forward to seeing the future of odronextamab, as well.

Dr. Ayyappan: Thank you.

About Dr. Ayyappan

Sabarish Ayyappan, MD, is the Director of Hematological Malignancies and an Assistant Professor of Medicine at the City of Hope Cancer Center in Atlanta, Georgia. Dr. Ayyappan's clinical and research interest revolve around hematologic malignancies, and he is an active participant and leader in studies investigating novel therapies.

For More Information

Ayyappan S, Kim W, Kim T, et al (2023). Final analysis of the phase 2 ELM-2sStudy: odronextamab in patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL). Presented at: 2023 American Society of Hematology Annual Meeting. Abstract 436. Available at: https://ash.confex.com/ash/2023/webprogram/Paper179818.html

Transcript edited for clarity. Any views expressed above are the speaker's own and do not necessarily reflect those of Oncology Data Advisor. 


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