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ELM-2 Trial Indicates Odronextamab Effective, Safe in Patients With Follicular Lymphoma
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Building off the positive results of ELM-1, the ELM-2 trial found intravenously administered odronextamab was safe and effective in patients with relapsed or refractory follicular lymphoma.
In a clinical trial, odronextamab, a CD20xCD3 bispecific antibody that destroys malignant B cells, demonstrated high complete response rates (CRR) and showed a manageable safety profile in patients with heavily pretreated relapsed or refractory follicular lymphoma (R/R FL), according to study results published in Annals of Oncology.1
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FL is the most common form of non-Hodgkin lymphoma (NHL), and chemoimmunotherapy is the typical treatment protocol for patients. However, many patients inevitably relapse, with worsening outcomes for each successive relapse.1
In the ELM-1 phase 1 trial, odronextamab was given to patients with heavily pretreated B-NHL subtypes. The trial demonstrated that odronextamab was active at doses of ≥5 mg for indolent lymphoma.2
Furthermore, the objective response rate (ORR) in patients with FL who received odronextamab was 91% (95% CI, 75-98%), while the CRR was 72% (95% CI, 53-86%). These positive results have informed the investigators in their current ELM-2 phase II study, in which they sought to report the primary analysis of odronextamab in patients with R/R FL.1,2
The primary end point was ORR, assessed by an independent central review (ICR) team. Secondary end points include complete response (CR) rate, duration of response (DOR), progression-free survival, and overall survival.1
In total, 128 patients with R/R FL enrolled at 49 sites between December 2019 and July 2022. At the time of data cut-off, 29 patients remained on treatment; common reasons for treatment discontinuation were disease progression (25%) and adverse events (AEs; 16%).1
Efficacy data was analyzed at 20.1 months. The primary end point of ORR evaluated by the ICR team was 80% (103/128; 95% CI, 72.5-86.9%), and the CR was 73%; importantly, 90% of responders achieved CR. Per the local investigator’s analysis, the ORR and CR rate were 82% and 73%, respectively.1
By the time of the first planned assessment at week 12, 91 of 103 (88%) responders had achieved at least a partial response. The overall median time to a patient’s first response was 2.7 months, while median DOR was 22.6 months.1
Across all prespecified subgroups, odronextamab demonstrated strong efficacy marks. There were consistent effects in high-risk patients, especially those with POD24 (ORR, 81%; CR rate, 73%) and prior ASCT (ORR, 85%; CR rate, 77%) and those who received ≥4 or ≥5 lines of therapy prior to enrollment in the trial.1
Not only did odronextamab meaningfully reduce the size of patient’s tumors, but patients receiving the drug consistently reported maintaining a good quality of life and functioning. Furthermore, over 60% of patients reported maintenance or clinically meaningful improvement in patient-reported outcomes.1
Regarding safety, treatment-emergent AEs (TEAEs) appeared in all patients, with 118 (92%) of patients experiencing at least 1 treatment-related TEAE. The most common were cytokine release syndrome (CRS; 56%), neutropenia (39%), and pyrexia (38%). However, there were low rates of dose reduction (9%) or treatment discontinuation (8%) due to treatment-related AEs.1
The safety profile in ELM-2 is very similar to that of ELM-1, in which the investigators reported serious AEs in 61% of patients. Frequently reported AEs included CRS (28%), pyrexia (8%) and pneumonia (6%). CRS and other neurological TEAEs were considered low grade and did not result in treatment discontinuation.2
ELM-2 demonstrated strong and comparable efficacy and safety data, building off of the positive results of ELM-1 and demonstrating a potentially new treatment option for patients with R/R FL. The investigators concluded by advocating for further investigation of the drug in patients with FL, as a monotherapy and in combination with other agents.1,2
References
1. Kim TM, Taszner M, Novelli S, et al. Safety and efficacy of odronextamab in patients with relapsed or refractory follicular lymphpma. Annals of Oncology. Published online. 2024-08-13. doi:10.1016/j.annonc.2024.08.2239
2. Bannerji R, Arnason J, Advani RH, et al. Odronextamab, a human CD20×CD3 bispecific antibody in patients with CD20-positive B-cell malignancies (ELM-1): results from the relapsed or refractory non-Hodgkin lymphoma cohort in a single-arm, multicentre, phase 1 trial. Lancet Hematol. 2022;9(5):e327-e339. doi:10.1016/S2352-3026(22)00072-2
