Odronextamab Shows Efficacy, Safety in R/R DLBCL After Progression Post–CAR T-Cell Therapy

Odronextamab (Ordspono), a CD20 x CD3 bispecific antibody, produced durable responses and had a manageable safety profile in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) who experienced disease progression after CAR T-cell therapy, according to results from the primary analysis of the phase 1 ELM-1 study (NCT02290951) published in Blood and presented at the 2024 ASH Annual Meeting.1,2

Findings showed that at a median follow-up of 16.2 months (95% CI, 8.0-17.6), evaluable patients (n = 60) achieved an overall response rate (ORR) of 48.3% (95% CI, 35.2%-61.6%), including a complete response (CR) rate of 31.7% (95% CI, 20.3%-45.0%).

The most common treatment-emergent adverse effect (TEAE) was cytokine release syndrome (CRS), occurring in 48.3% of patients, although no grade 3 or higher CRS was reported. Notably, no cases of immune effector cell–associated neurotoxicity syndrome (ICANS) were observed.

"We found that odronextamab is safe and effective post–CAR T-cell therapy with approximately half of patients responding. Patients who achieve a CR can have excellent and durable responses, suggesting that this potentially has a future role in helping [treat] patients after relapse following CAR T-cell therapy,” Matthew Matasar, MD, said in an interview with OncLive®.

Matasar serves as chief of the Division of Blood Disorders at Rutgers Cancer Institute; a hematologist/oncologist; and professor of medicine at Rutgers Robert Wood Johnson Medical School in New Brunswick, New Jersey.

ELM-1 Study Design and Rationale

In this expansion cohort of the open-label, multicenter ELM-1 trial, investigators enrolled patients at least 18 years of age with relapsed or refractory DLBCL who had received at least 2 prior lines of systemic therapy, had an ECOG performance status of no more than 1, and had measurable disease per Lugano criteria. Disease progression following prior CAR T-cell therapy was required.

"We know that CAR T-cell therapy has changed the landscape of LBCL; however, despite that, approximately only one-third of patients will be cured by CAR T-cell therapy. Those who are not cured do represent a significant unmet need,” Matasar explained.

Enrolled patients received odronextamab in a step-up dosing regimen of 1/20 mg to 0.7/4/20 mg during the first 21-day cycle, then 160 mg on days 1, 8, and 15 of cycles 2 to 4, and 320 mg once every 2 weeks thereafter until disease progression or unacceptable toxicity. Those who achieved a CR that persisted for at least 9 months transitioned to receiving odronextamab at 320 mg once every 4 weeks.

The primary end point of the trial was ORR, as assessed by an independent central review committee assessment. Secondary end points included duration of response (DOR), CR rate, duration of CR (DOCR), progression-free survival (PFS), overall survival (OS), time to response per Lugano criteria, and minimal residual disease–negativity rate.

The study also evaluated safety outcomes, including overall frequency of AEs and dose-limiting toxicities with a follow-up period of up to 24 months for safety assessments.

Enrolled patients had a median age of 63 years (range 27-82). CAR T-cell therapies received prior to enrollment were axi-cel (60%), tisa-cel (16.7%), liso-cel (10%), and an investigational CD19-directed product (13.3%). The median time since prior CAR T-cell therapy was 6.5 months (range 1.2-46.2). In total, patients received a median of 3 prior lines of therapy (range 2-9). Additionally, 76.7% of patients had disease that was refractory to the last line of therapy,

Notably, 48.3% of patients relapsed within 90 days of prior CAR T-cell therapy, and 66.7% relapsed within 180 days.

Additional Efficacy and Safety Findings

Responses were observed across different CAR T-cell products and regardless of time to relapse post-CAR T therapy. The median DOR was 14.8 months, and the median DOCR was not reached.

The median PFS was 4.8 months (95% CI, 2.6-5.4), and the median OS was 10.2 months (95% CI, 4.6-15.8).

Treatment-related TEAEs led to treatment discontinuation in 8.3% of patients. Two patients (3.3%) experienced grade 5 AEs.

Any-grade infections were reported in half of patients, and grade 3 or more infections occurred in 20.0% of patients, including two instances of COVID-19. Additionally, 3 patients 5.0%) discontinued treatment due to infections.

"There were infectious complications, as would be expected in this patient population, post–CAR [T-cell therapy]. We know that bispecific [antibodies] in general do have immunosuppressive qualities, so we continue to understand that management and mitigation of infectious risks is important," Matasar noted.

References

1. Topp MS, Matasar MJ, Allan JN, et al. Odronextamab monotherapy in R/R DLBCL after progression with CAR T-cell therapy: Primary analysis of the ELM-1 study. Blood. Published online December 30, 2024. doi:10.1182/blood.2024027044
2. Matasar MJ, Topp MS, Allan JN, et al. Efficacy and safety of odronextamab monotherapy in patients (Pts) with diffuse large B-cell lymphoma (DLBCL) progressing after CAR T-cell therapy: primary analysis from the ELM-1 study. Blood. 2024;144(suppl 1):866. doi:10.1182/blood-2024-199155