ELM-2 Trial Indicates Odronextamab Effective, Safe in Patients With 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