SOHO 2025 | Long-term follow-up results from ELM-2: odronextamab in R/R FL

This study evaluates long-term follow-up of the Phase II ELM-2 study, looking at the efficacy and survival outcome of patients treated with the bispecific odronextamab in relapsed/refractory lymphoma. The background is that patients with follicular lymphoma are a patient population with an unmet need, and oftentimes their outcomes are quite poor, so therefore there’s a strong need for newer therapies with less side effects. Odronextamab is an off-the-shelf CD20-CD3 bispecific antibody and has demonstrated remarkable efficacy and a manageable side effect profile in heavily pretreated relapsed/refractory follicular lymphoma patients. And that was published already from the Phase II study of the ELM-2 study, and the follow-up has been at the time of publication 20.1 months. And so this is a long-term survival outcome from the same study with over two years of follow-up. So the background of the study has been published already, but just to reiterate, this was a Phase II multi-cohort, multi-center study that included various types of relapsed B-cell histology, but here we’re focusing just on the follicular lymphoma cohort. The key eligibility criteria were pretty standard with age greater than 18 years. Follicular lymphoma grade 1 to 3, good performance status, and they’ve had to have had at least two prior lines of therapy, including a CD20 antibody and an alkylating agent, pretty standard eligibility criteria. Odronextamab was administered intravenously in a step-up fashion during cycle one, and then given weekly during cycles two through four, and then every other week thereafter with every four week administration available for patients who accomplish a complete remission at cycle nine. The primary endpoint was overall response rate and there were several secondary endpoints including CR rate, duration of response, progression-free survival, overall survival and safety, tolerability. There were also exploratory endpoints with minimal residual disease and other biomarkers. The baseline characteristics of this patient population was representative of what we usually encounter in clinics. So 128 patients were enrolled in this cohort. Median age was 61, median prior lines of therapy was three. About half of the patients had a high FLIPI score and the majority of patients were refractory to the last line of therapy. And a marker that has been established in the few couple of years of difficult to treat follicular lymphoma was the POD24 patients – progressed within 24 months – and about half of the patients were falling into this category. So in this updated analysis, the median progression-free survival was 23 months. Of note, patients who accomplished a complete remission accomplished a longer progression-free survival of 34.5 months, which is not altogether surprising. But those who did not only had a progression-free survival of 9.9 months. The responses were durable with a median duration of response of 26 months. And then the overall response rates were 80.5%, with a CR rate of 74.2%, so slightly higher CR rate than what’s been published in their recent analysis, in the initial analysis. The overall survival median, again, was 54.2 months. And that was similar also for the patients who accomplished the CR. However, those who did not, the median overall survival was only 18.4 months. So there’s still work that needs to be done. This study also looked at progression-free survival by ctDNA status, and those patients who accomplished negative ctDNA status had a progression-free survival of 42.4 months, whereas those who did not only half the time was accomplished in terms of progression-free survival with 21.6 months, establishing ctDNA as a potential surrogate for duration of response in this patient population in that study. The study was overall well-tolerated. There were a number of adverse events, but nothing that stood out as new or unexpected, the most common being CRS that, you know, occurred in over half of the patients. However, most of the CRS was grade 1, 2, so mild and almost more percentage had grade 3, 4. There was no grade 5 CRS observed. Other side effects included neutropenia, fevers, anemia, and then also, of course, COVID-19, given that the study was conducted to the height of the pandemic. There were some infectious-related deaths, unfortunately, as well. Three patients had fatal infectious complications with E. coli, sepsis, and then also pneumonia and systemic fungal infection. But again, sort of nothing unexpected given how heavily pretreated these patients have been and immunocompromised. So in summary, with long-term follow-up, the treatment with odronextamab demonstrated deep and durable responses in this heavily pretreated patient population with an overall response rate of 80% and CR rate of just a bit over 74%. Median duration of patients in CR was 32.2 months. And overall, CR rates were consistent across many high-risk groups. I didn’t go into that, but there was no significant difference in these patient populations. Median progression-free survival, again, was 23 months with a median overall survival of greater four years. So overall, these results are pretty compelling and sort of in line with what has been described for other bispecifics in that field. And yeah, so hopefully this will be another bispecific that will become available in the US for treatment for patients with relapsed refractory follicular lymphoma. Thank you very much.

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