KEY TAKEAWAYS
- The phase 2 ELM-2 study investigated the effects of odronextamab on adult patients diagnosed with Follicular Lymphoma Grade 1–3a, who relapsed or were unresponsive to at least two prior treatments.
- The study’s primary endpoint was the ORR.
- The study found that odronextamab is effective for patients with relapsed or refractory FL. Using the optimized 0.7/4/20 step-up regimen, the drug showed an acceptable safety profile.
The ELM-2, a multi-center research study, involved adult patients (pts) diagnosed with Follicular Lymphoma (FL) Grade 1–3a who were relapsed or refractory (R/R) to treatment after undergoing at least two prior lines of therapy (LOT), including the use of an anti-CD20 antibody and an alkylator. IV odronextamab was given in 21-day cycles by steroid prophylaxis and a step-up dosing approach during the first cycle (Cycle 1). The initial step-up regimen included 1 mg of the medication, split between Cycle 1 Day 1 (C1D1) and Cycle 1 Day 2 (C1D2), followed by 20 mg between C1D8 and C1D9. Subsequently, the full 80 mg dose was given on Cycle 1, Day 15 C1D15, following the 1/20 regimen.
The treatment plan was modified during the study to decrease the risk of cytokine release syndrome (CRS). The revised regimen involved the distribution of 0.7 mg, divided between C1D1(0.2 mg) and C1D2(0.5 mg), 4 mg split over C1D8 and C1D9, and 20 mg split between C1D15 and C1D16. Subsequently, the full 80 mg dose was administered on C2D1, following the 0.7/4/20 regimen. The 80 mg dose continued weekly until the conclusion of Cycle 4, then increased to 160 mg every two weeks (Q2W) until either the progression of the disease or unacceptable toxicity. The objective response rate (ORR) assessment was the primary endpoint, evaluated through an independent central review (ICR). The response data presented here are based on the ICR evaluation.
As of September 15, 2022, 131 pts underwent treatment with a median age of 61 years (range of 22 to 84 years), with 53% being male. Patients received three prior lines of therapy (range 2 -13), 71% refractory to most recent treatment, and 48% of the pts experienced disease progression within two years. The median duration of follow-up was 22.4 mos. Objective response rate (ORR) and complete response (CR) rate, as per ICR, were 82% (99/121) and 75% (91/121), consistent across high-risk subgroups. The responses were stable, with a median duration of response and a median period of CR lasting for 20.5 mos. The median progression-free survival (PFS) was 20.2 months (95% CI 14.8–not estimable [NE]), and the median OS was not reached (95% CI NE–NE).
Adverse events related to treatment occurred in all pts and were associated with treatment in 118 cases (90%). There were reports of Grade 5 treatment-related adverse events (TEAEs) in three pts (pneumonia, progressive multifocal leukoencephalopathy, and systemic mycosis, with one case each) due to TEAEs, and ten patients discontinued treatment. The most frequently observed TEAEs (over 30% of all grades) were cytokine release syndrome (CRS), affecting 56% of pts, neutropenia in 40% of pts, and pyrexia in 31% of pts. In the subgroup of pts who followed the 0.7/4/20 step-up regimen (63 pts), there was one occurrence of Grade 3 CRS (no Grade 4 or 5 CRS events were reported, and all CRS events resolved), and no cases of immune effector cell-associated neurotoxicity syndrome (ICANS) were documented.
The ELM-2 study demonstrated that odronextamab exhibited significant effectiveness in pts with R/R FL and maintained an acceptable safety profile when utilizing the refined 0.7/4/20 step-up regimen. For this particular group of pts with insufficient prognosis, odronextamab could offer a more accessible treatment option with a promising benefit-risk compared to currently available therapies.
Source: https://onlinelibrary.wiley.com/doi/10.1002/hon.3163_82
Clinical Trial: https://classic.clinicaltrials.gov/ct2/show/NCT03888105
Novelli, S., Luminari, S., Taszner, M., Cho, S., Le Gouill, S., Poon, M., Villasboas, J.C., Champion, R., Bachy, E., Guidez, S., Alonso, A., Jagadeesh, D., Merli, M., Tucker, D., Cai, J., Leite de Oliveira, C., Zhu, M., Chaudhry, A., Mohamed, H., Ambati, S. and Kim, T.M. (2023), ODRONEXTAMAB IN PATIENTS WITH RELAPSED/REFRACTORY FOLLICULAR LYMPHOMA (FL) GRADE 1–3A: RESULTS FROM A PRESPECIFIED ANALYSIS OF THE PIVOTAL PHASE II STUDY ELM-2. Hematological Oncology, 41: 121-122. https://doi.org/10.1002/hon.3163_82
