A population of patients with highly refractory follicular lymphoma achieved longstanding responses, with few significant adverse events, from odronextamab monotherapy, according to findings of the ELM-2 study. The study outcomes were published by Tessoulin et al in Clinical Lymphoma, Myeloma & Leukemia.
Of the 128 patients in the study, 80% achieved an objective response rate, with 73% achieving a complete response. The progression-free survival was 20.7 months.
“For patients who achieved a complete response, it appears that they’re able to sustain that response for a long period of time,” said study coauthor Deepa Jagadeesh, MD, Vice-Chair of Quality and staff physician in the Department of Hematology and Medical Oncology at Cleveland Clinic Cancer Institute.
Background
Follicular lymphoma is typically indolent, but patients who experience disease progression within 2 years of initial treatment as well as those who are refractory to rituximab tend to have poor outcomes. Many patients with relapsed/refractory disease also struggle with lymphadenopathy, fevers, fatigue and weight loss. With each subsequent therapy, patients tend to have shorter periods of remission, so more effective therapies are needed.
ELM-2 Study Design
This phase II multicenter study investigated the safety and efficacy of the CD20 x CD3 bispecific antibody odronextamab, primarily among patients with advanced-stage disease or intermediate- to high-risk characteristics. Half of the patients in the study had relapsed within 2 years of initial treatment. Roughly 74% were refractory to an anti-CD20 antibody and approximately 40% were refractory to an alkylator as well as an anti-CD20 antibody.
For the study, odronextamab was administered intravenously in 21-day cycles in step-up dosing:
- 0.7/4/20 mg on days 1/2, 8/9, and 15/16 (the initial regimen started with 1/20 mg but was modified to 0.74/20 mg to lower the risk of cytokine-release syndrome).
- 80 mg weekly on cycles 2-4
- 160 mg every 2 weeks for cycles 5 and beyond
- Patients who achieved a durable complete response for more than 9 months were moved to a regimen of 160 mg every 4 weeks.
The median duration of treatment was 31 weeks. The primary endpoint was overall response rate by an independent review committee, with secondary endpoints being duration of response, progression-free, overall survival, as well as safety and tolerability.
Results
Odronextamab demonstrated high rates of durable response with an overall manageable safety profile. At a median follow-up of 20.1 months, the overall response rate was 80%, with a complete response rate of 73%. The median duration of complete response was 25.1 months, median progression-free survival was 20.7 months, and median overall survival was more than 4 years.
Patients also reported improved quality of life and functional status, based on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30. Improved physical and emotional functioning continued through 50 weeks.
Adverse events were generally manageable. The most common side effects were cytokine-release syndrome (56%), neutropenia (39%), and pyrexia (38%). Most instances of cytokine-release syndrome were grade 1, occurring during the first cycle and resolving without incident. Only one patient experienced grade 2 immune effector cell–associated neurotoxicity syndrome.
There were high rates of infection, including eight patients who died due to COVID-19. Some patients had received up to 13 lines of therapy prior to the study, and roughly one-third had undergone an autologous stem cell transplant before.
“When giving treatments like [chimeric antigen receptor] T-cell therapy or bispecifics to highly immunosuppressed patients, we are noticing higher infection rates, so that’s something to watch for,” noted Dr. Jagadeesh.
Additional Points
Data at the 12-week follow-up point showed patients with undetectable circulating tumor DNA had slightly longer progression-free survival. However, researchers would like to understand if this trend will continue over a longer follow-up period.
Odronextamab is approved for use in Europe and is under U.S. Food and Drug Administration review.
“There are already two other bispecifics approved to treat follicular lymphoma—[mosunetuzumab and epcoritamab]—so the question is how do physicians pick one over the other,” said Dr. Jagadeesh. “Less toxicity, higher efficacy, and less financial toxicity are factors they would influence this decision. For this therapy, the [cytokine-release syndrome] rate was very low with step-up dosing. However, the study did require hospitalization for cycle one, and that may be a barrier for some patients. It would be encouraging if we had data in the future showing the medication could be administered on an outpatient basis.”
Researchers would like to better understand if odronextamab could be given as a time-limited treatment rather than continuously to reduce the financial impact as well as the risk of infection.
The study authors concluded, “In this heavily pretreated, highly refractory population, maintenance or improvement of health-related quality of life, functioning, and symptoms support odronextamab as a potential treatment option in relapsed/refractory follicular lymphoma.”
DISCLOSURE: For full disclosures of the study authors, visit clinical-lymphoma-myeloma-leukemia.com.
