Elizabeth A. Brem, MD, is an associate clinical professor of medicine at the University of California Irvine.

Elizabeth A. Brem, MD, highlights upcoming changes in the follicular lymphoma treatment paradigm that could move the field beyond chemotherapy.

Dr Brem on the Potential Shift Away From Chemotherapy in Follicular Lymphoma

“[Looking at the] big picture, we are entering an era in follicular lymphoma [with] bispecific antibodies, CAR T-cell therapies, and many of us have been using lenalidomide-based therapies for years. I think there’s a good chance that in the next few years, we’re not really going to be using chemotherapy for follicular lymphoma.”

Elizabeth A. Brem, MD, associate clinical professor, medicine, University of California Irvine, highlights prospective treatment paradigm changes in patients with follicular lymphoma following safety lead-in data from the phase 3 OLYMPIA-1 trial (NCT06091254), noting the potential to move away from chemotherapy for this patient population.

Data from the safety lead-in portion (part 1) of the OLYMPIA-1 trial evaluating the CD20 and CD3 bispecific antibody odronextamab as monotherapy in patients with previously untreated grade 1 to 3 follicular lymphoma demonstrated that outpatient administration of the agent was deemed feasible. In the randomized portion of the study, patients are being randomly assigned to receive odronextamab or rituximab (Rituxan) plus investigator’s choice of chemotherapy backbone.

Although odronextamab is not currently FDA-approved for patients with follicular lymphoma, adding newer treatments, such as bispecific antibodies and CAR T-cell therapies, can help improve the follicular lymphoma treatment paradigm, Brem begins.

In part 1 of the OLYMPIA-1 trial, no dose-limiting toxicities (DLTs) or immune effector cell-associated neurotoxicity syndrome (ICANS) were observed (n = 13). Of note, all instances of cytokine release syndrome (CRS) were grade 1, and 100% of DLT-evaluable patients achieved complete remission at week 12 assessment. No grade 4/5 infections were reported; however, grade 3 infections occurred in 2 patients.

Any-grade treatment-emergent adverse effects (TEAEs) occurred in all patients; grade 3 or greater TEAEs were observed in 46.2% of patients, and serious TEAEs were reported in 38.5%. The most common TEAES included CRS (61.5%), diarrhea (46.2%), and rash (38.5%). One patient discontinued treatment due to elevated levels of liver enzymes, which emerged from treatment.

Brem notes that ongoing studies, including OLYMPIA-1, have shown that these newer therapies engage the immune system well—especially in early lines of treatment. In the next few years, the use of chemotherapy in follicular lymphoma could decrease as newer therapies continue to demonstrate improved efficacy, she concludes.

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“Overall, we were very encouraged by the efficacy. We're really eager to see how that translates into progression-free survival, and the overall safety and tolerability looked really excellent, as well.”

Elizabeth A. Brem, MD, associate clinical professor, medicine, University of California Irvine, discusses results from the safety lead-in portion of the phase 3 OLYMPIA-1 trial (NCT06091254) evaluating odronextamab monotherapy in previously untreated patients with high-risk follicular lymphoma. The initial analysis presented at the 

 focused on patients (n = 13) receiving odronextamab to assess safety and early efficacy prior to advancing into the randomized phase of the study.

Data demonstrated that odronextamab administered in an outpatient setting was feasible and well-tolerated. No dose-limiting toxicities (DLTs) were observed. Cytokine release syndrome (CRS) occurred in 61.5% of patients; however, all instances of CRS were grade 1.

Importantly, no instances of immune effector cell–associated neurotoxicity syndrome (ICANS) were reported. Grade 3 infections were reported in 2patients (15.4%), but no grade 4 or 5 infections occurred, and no patients discontinued therapy due to infection-related adverse effects.

Efficacy data showed that the overall response rate (ORR) and complete response (CR) rate were both 92.3%. Notably, the only patient (7.7%) to not achieve a response was not evaluable. The median duration of response was 3.1 months (95% CI, 2.8-5.6).

Enrollment for Part 2 of the OLYMPIA-1 trial is ongoing using a recommended phase 3 dose of odronextamab at 80 mg, based on findings from the safety lead-in. The randomized portion of the study is evaluating odronextamab vs rituximab (Rituxan) plus chemotherapy induction, followed by rituximab maintenance.

Elizabeth Brem, MD, discusses data for odronextamab monotherapy in previously untreated patients with high-risk follicular lymphoma.

Elizabeth A. Brem, MD

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