Odronextamab showed good clinical efficacy and a generally manageable safety profile in heavily pretreated patients with relapsed or refractory (R/R) marginal zone lymphoma (MZL). Tae Min Kim, MD, PhD, a professor of internal medicine at Seoul National University Hospital in South Korea, reported at the 66th American Society of Hematology Annual Meeting and Exposition that the responses were durable, with 80.2% of patients maintaining response at one year. All cytokine release syndrome (CRS) events were grade 2 or lower, and the overall safety profile with R/R MZL was consistent with that observed in the follicular lymphoma cohort.
Dr. Kim said the ELM-2 study now has 29 evaluable patients with R/R MZL and is still recruiting patients. The median age of enrolled patients is 63.5 years (range = 34-82), and approximately half are male. Patients had received a median of two prior lines of therapy; 64.3% were refractory to their last treatment, 47.6% were refractory to the anti-CD20 antibody in any line, and 33.3% were double refractory to alkylator/anti-CD20 antibody in any line.
Patients received a step-up regimen: cycle one was intravenous odronextamab with steroid prophylaxis; cycles 2-4 were odronextamab 80 mg on days 1, 8, and 15; and post-cycle 4 was a maintenance dose of 160 mg odronextamab every two weeks until disease progression or unacceptable toxicity. The median follow-up was 11.1 months for the efficacy population. Median odronextamab exposure was 26.2 weeks; 88.1% of patients completed one or more cycles, and 64.3% completed four or more cycles.
Dr. Kim reported that the objective response rate was 77.1%, and the complete response (CR) rate was 77.1%. He explained that “after final analysis, the response rate may be somewhat decreased,” but he nevertheless called the preliminary results “very surprising.”
The study did not reach a median duration of response, median duration of CR, or progression-free survival (PFS). The 12-month PFS rate was 87.5%. “I don’t know why the MZL population has the superior outcome,” Dr. Kim said, explaining that his team struggled to understand the mechanism behind the surprising efficacy of odronextamab for patients with R/R MZL.
Most patients (83.3%) experienced a grade 3 or higher treatment-emergent adverse events (TEAEs). The most common TEAEs (any grade) were CRS (54.8%), neutropenia (31.0%), and pyrexia (35.7%). Four patients (9.5%) discontinued treatment due to TEAEs. CRS occurred in 56.5% of patients who received the optimized step-up regimen with steroid prophylaxis. All CRS events were grade 1 or 2; the team reported no occurrences of immune effector cell-associated neurotoxicity syndrome. Approximately one-quarter (23.8%) of patients experienced grade 3 infections, and no patients in the cohort experienced grade 5 infections.
While not approved for use in the U.S., odronextamab was approved in August in the European Union as a treatment for adult patients with R/R follicular lymphoma or R/R diffuse large B-cell lymphoma after two or more lines of systemic therapy. The approval was based on results from the phase I ELM-1 and pivotal phase II ELM-2 trials. Dr. Kim concluded that the analysis of data from patients with R/R MZL suggests that odronextamab has the potential to be an important treatment option for them as well, and the ELM-2 results are promising enough to justify pursuing a phase III trial.
Any conflicts of interest declared by the authors can be found in the original abstract.
Reference
Kim TM, Cho S-G, Taszner M, et al. Efficacy and safety of odronextamab in relapsed/refractory marginal zone lymphoma (R/R MZL): data from the R/R MZL cohort in the ELM-2 study. Abstract 862. Presented at the 66th American Society of Hematology Annual Meeting and Exposition on December 9, 2024, in San Diego, California.
