Sandoz rituximab (SDZ-RTX) is approved in Europe, Japan, Australia, and New Zealand for use in all indications of reference rituximab. Approval was based on the totality of evidence for biosimilarity, including extensive physicochemical and structural data, as well as preclinical and clinical pharmacokinetic, pharmacodynamic and immunogenicity data, and also clinical trials including a Phase III confirmatory trial in patients with follicular lymphoma. REFLECT is the first post-approval study for a rituximab biosimilar in diffuse large B-cell lymphoma (DLBCL). REFLECT is a prospective, non-interventional, open-label study of the effectiveness and safety of SDZ-RTX as curative therapy in patients with treatment-naïve CD20+ DLBCL.
To report study design and interim baseline patient demographics and safety data to September 6, 2018, when recruitment was approx. 50% complete.
The study includes patients aged ≥18 years with CD20+ DLBCL, eligible for treatment with rituximab and cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP). Exclusion criteria include any prior DLBCL treatment or contraindication to rituximab. R-CHOP is administered according to product label. The primary endpoint is complete response rate, assessed by the treating physician at the end of treatment. Secondary endpoints include: overall response rate; 12-month progression-free survival; quality of life; and adverse events (AEs). Data are collected at baseline, and at every study visit for 12 months (efficacy) and until ≥30 days after the last SDZ-RTX dose (safety). No imputation for missing data is planned and endpoints are summarized descriptively.
The interim full analysis set comprised 80 patients, of which 38 were male (48%) and 42 were female (53%). Median age was 68.5 years and 70% of patients were aged ≥60 years. In total, 6 patients (8%) have discontinued the study. Median baseline BMI was 25 (min 20, max 48), and mean time from diagnosis to start of treatment was 1.5 months (SD 5.1). Most patients had little or no restriction in daily activities, with >80% of patients having an ECOG score of 0 (34%) or 1 (50%). No ECOG score >2 was observed. Similar results were observed on the Karnofsky performance scale: 76% of patients scored ≥80%. The most commonly reported baseline symptoms were enlarged lymph nodes (n = 48, 60%) and disease-related pain (n = 21, 26%). B symptoms were reported in 15 patients (19%). Extranodal infiltration was observed in 40 patients (50%), bulky disease in 9 patients (11%), and spleen involvement in 2 patients (3%). Early-stage disease (0–IIB) was reported for 64% of patients, and low-to-intermediate risk disease (IPI 0–2) for 61% (Table).
Safety is summarized in the Table. AEs were reported in 53 patients (66%), serious AEs were reported in 19 patients (24%), and treatment-related AEs were reported in 13 patients (16%). The most frequent AEs were polyneuropathy (n = 10, 13%), anemia (n = 8, 10%), and fatigue (n = 8, 10%).
REFLECT provides the first prospective real-world data for a rituximab biosimilar and CHOP as a curative therapy for CD20+ DLBCL. In this interim analysis, baseline patient data and disease characteristics were as expected for treatment-naïve patients with CD20+ DLBCL, and safety was as expected for rituximab-based treatment. Recruitment is ongoing and expected to be completed by March 2019. Biosimilar rituximab has the potential to provide savings for healthcare systems and broaden patient access to rituximab-based chemotherapy, supporting the sustainability of cancer care.