Odronextamab ‘potentially curative’ in third-line setting for follicular lymphoma
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NEW ORLEANS — Odronextamab showed promising efficacy among patients with grade 1 to grade 3a follicular lymphoma who received two or more prior lines of therapy, according to study results presented at ASH Annual Meeting and Exposition.
Three-quarters of patients in the cohort achieved complete remission with the hinge-stabilized, human immunoglobulin G4-based CD20 x CD3 bispecific antibody, which also exhibited an acceptable safety profile.
“Odronextamab [REGN1979, Regeneron] is a potentially curative treatment option in the third-line setting for follicular lymphoma,” Tae Min Kim, MD, PhD, associate professor of internal medicine at Seoul National University Hospital in Seoul, Republic of Korea, told Healio.
Background
Odronextamab binds CD3 on T cells and CD20 on B cells, resulting in T-cell-mediated cytotoxicity of malignant B cells, according to study background.
“CD20 x CD3 bispecifics alone showed promising anti-lymphoma activity in patients who failed two prior second-line treatments,” Kim said.
In the ELM-1 trial, heavily pretreated patients with grade 1 to grade 3a follicular lymphoma who received odronextamab at doses of 5 mg or higher had an objective response rate of 91% and complete response rate of 72%. The 4-year PFS rate of 54% showed durability of responses.
The trial established a recommended dose of 80 mg for expansion among this patient population.
Methodology
The multicenter, global ELM-2 trial evaluated a step-up regimen of odronextamab, administered in 21-day cycles with steroid prophylaxis, designed to preserve efficacy while reducing acute toxicity, including risk for cytokine release syndrome (CRS). The 1/20 step-up regimen was modified during cycle 1 to a 0.7/4/20 regimen to further mitigate CRS risk.
Objective response rate according to Lugano 2014 criteria and assessed by independent central review served as the primary endpoint.
At data cutoff Sept. 15, 131 patients (median age, 61 years; 38.9% aged 65 years; 53.4% male) were eligible for safety analysis. Among them, 30.5% had prior autologous hematopoietic stem cell transplant. Most (71%) were refractory to their last treatment, 74.8% to prior anti-CD-20 therapy, and 48% experienced disease progression within 2 years.
Median follow-up was 22.4 months.
Key findings
Results showed an ORR of 81.8% (95% CI, 73.8-88.2) and complete response rate of 75.2% among 121 patients eligible for efficacy analysis. These rates appeared consistent at week 12 across high-risk patient subgroups and regardless of whether patients received the original vs. revised step-up regimen (ORR, 72.1% vs. 75.5%; complete response, 61.8% vs. 71.7%).
In addition, responses proved durable, with a median duration of response of 20.5 months (95% CI, 15.2 to not estimable) and median duration of complete remission of 20.5 months (95% CI, 16.8 to not estimable).
Kim reported median PFS of 20.2 months (95% CI, 14.8 to not estimable), and median OS had not been reached (95% CI, 23 months to not estimable).
At data cutoff, 42.7% of patients remained on treatment.
All 131 patients eligible for safety analysis experienced treatment-emergent adverse events, including 118 (90.1%) with events deemed treatment-related. The most common adverse events, most of which were low-grade, included CRS (56.5%), neutropenia (39.7), pyrexia (31.3%), anemia (29.8%) and infusion-related reactions (29%).
Treatment-related adverse events led to discontinuation of therapy for 7.6% of patients.
The revised step-up regimen reduced incidence of grade 2 (17.6% vs. 11.1%) and grade 3 (5.9% vs. 1.6%) CRS. All CRS events resolved within a median 2 days (range, 1-51).
No patients who received the revised regimen had immune effector cell-associated neurotoxicity syndrome, compared with one who received the original step-up regimen.
Clinical implications
Odronextamab could serve as a more accessible treatment option for patients with relapsed/refractory follicular lymphoma compared with chimeric antigen receptor T-cell therapy and other existing treatments, according to researchers. Kim emphasized the complete response rate and durability of complete responses in a heavily treated patient population with a typically poor prognosis.
“[We observed a] very high complete remission rate of 75.2% based on the updated data,” he told Healio.
References:
- Bannerji R, et al. Lancet Haematol. 2022;doi:10.1016/S2352-3026(22)00072-2.
- Kim TM, et al. Abstract 949. Presented at: ASH Annual Meeting and Exposition; Dec. 10-13, 2022; New Orleans.
Perspective
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Catherine S. Diefenbach, MD
Several take-home points can be derived from this abstract.
Step-up dosing of odronextamab mitigated CRS toxicity, decreasing the severity and incidence of CRS without impairing efficacy. Incidence of infusion reactions is quite high, though.
Efficacy remained high with a 75% complete response rate, which is extremely promising for a single agent in relapsed/refractory follicular lymphoma. However, the median PFS of 20 months is a bit surprising. Given the high complete response rate, the fact that the patients remain on treatment and that this is an indolent disease, I would have expected median PFS to be longer.
As this is pivotal phase 2 trial, odronextamab is likely on a registration track for approval in relapsed/refractory follicular lymphoma if this data can be confirmed in a randomized study.
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Kim TM, et al. Abstract 949. Presented at: ASH Annual Meeting and Exposition; Dec. 10-13, 2022; New Orleans.
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