mAbxience's RTXM83 Is Noninferior to Reference Rituximab in First-Line DLBCL

Spain-based drug maker mAbxience is developing a biosimilar rituximab, RTXM83. Last week, researchers reported findings from a head-to-head study of the proposed biosimilar versus its reference product as a first-line treatment for patients with diffuse large B-cell lymphoma (DLBCL).

The multicenter, double-blind, randomized study enrolled 272 newly diagnosed adult patients with DLBCL at 58 sites in 12 countries. Patients were randomized to receive either the reference or the biosimilar rituximab together with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy, and patients were followed for up to 9 months after their last study dose.

The primary efficacy endpoint was to compare overall response rate (ORR) in each treatment arm after cycle 6 or 30 days after the last study dose. Pharmacokinetics (PK), pharmacodynamics (PD), event-free survival (EFS), safety, and immunogenicity were secondary endpoints that were evaluated during treatment and follow-up.

In total, 85% of patients completed all 6 cycles of the study treatment. Exposure to rituximab was similar in the biosimilar and reference arms. In the 239 patients who comprised the intent-to-treat population, after 6 cycles of treatment, the investigators observed a 0.7% difference in ORR in favor of the biosimilar versus the reference (83.6% vs 82.9%), though this difference was not statistically significant. The lower bound of the 95% confidence interval of the difference was —8.77%, which was above the prespecified noninferiority margin of –13%.

Median EFS in the biosimilar and reference arms was similar (12.5 months vs 8.6 months, respectively; P =.4613). PK and PD measurements were also similar in both arms.

The proportion of patients with at least one treatment-emergent adverse event (AE) or serious AE was the same in each arm (96%), and the nature and frequency of AEs were in line with the known profile of rituximab in combination with CHOP. The most frequently reported AEs included hematologic toxicities, infections, and infusion-related reactions.

There was a low incidence of anti-drug antibodies (ADAs) in both treatment arms; 2.3% of patients in the biosimilar arm and 3.2% of those in the reference arm developed new ADAs.

According to the authors, this study—believed to be the first randomized, double-blind study of a biosimilar in patients with DLBCL—demonstrated the noninferiority of the biosimilar to the reference in terms of efficacy and supports the similarity of the 2 rituximab products.

Reference

Candelaria M, González DE, Delamain MT, et al. Rituximab biosimilar RTXM83 versus reference rituximab in combination with CHOP as first-line treatment for diffuse large B-cell lymphoma: a randomized, double-blind study [published online July 4, 2019]. Leuk Lymphoma. doi: 10.1080/10428194.2019.1633632.