In some patients, it will progress to the more aggressive diffuse large B-cell lymphoma (DLBCL); up to half of those with advanced disease will progress after first-line treatment.
Once relapsed or refractory, however, treatment options are limited and the prognosis is poor. A potential treatment for both subtypes is being investigated by Regeneron.
Odronextamab is a hinge-stabilised humanised IgG4 based bispecific antibody designed to bridge CD20 on cancer cells with CD3-expressing T cells.
A single arm Phase I dose escalation and expansion study was done in 145 heavily pretreated patients with relapsed/refractory CD20 positive B-cell non-Hodgkin lymphoma who had previously received CD20-directed antibody therapy.1
Patients were given odronextamab in a step-up dosing schedule during the first 3-week cycle, with doses ranging from 0.1–320 mg in cycles 2–4. Maintenance treatment was then given every 2 weeks until disease progression or unacceptable toxicity occurred.
No dose-limiting toxicities were observed; cytokine release syndrome (CRS) was the most common serious adverse event. The recommended dose for expansion was 80 mg for FL and 160 mg for DLBCL.
In patients with DLBCL given at least 80 mg doses, the objective response rate was 53% (all complete) if they had previously received CAR T cell therapy, and 33% (27% complete) if they had not.
A Phase II study is ongoing in more than 500 patients who had received at least two prior lines of treatment, including an anti-CD20 antibody and an alkylating agent. Subjects were given intravenous odronextamab in 21-day cycles, with steroid prophylaxis and weekly step-up dosing to try to reduce the risk of CRS (up to 160 mg).
After the fourth cycle, maintenance treatment was 320 mg every 2 weeks until disease progression or unacceptable toxicity. In a cohort of 96 patients with relapsed or refractory FL (severity from grade 1 to grade 3a), the objective response rate was 82%; 75% achieved a complete response.2
The median duration of complete response was 20.5 months and the median progression-free survival was 20 months. Median overall survival was not reached and CRS was the most common adverse event, followed by pyrexia, anaemia and infusion-related reactions; the CRS resolved with appropriate support.
Meanwhile, in 121 patients with relapsed/refractory DLBCL, the objective response rate was 53% and the complete response rate was 37%.3 The complete responses were durable with the median duration not reached. The most common treatment-emergent adverse events were CRS, pyrexia and anaemia. A Phase III trial is being initiated.
References
- R. Bannerji, et al., Lancet Haematol. 9, e327 (2022).
- W-S. Kim, et al., ASH Annual Meeting and Exposition 2022 (New Orleans, LA, US, 10–13 December 2022) Abstr. 444.
- T-M. Kim, et al., ASH Annual Meeting and Exposition (New Orleans, LA, US, 10–13 December 2022) Abstr. 949.
