Proposed rituximab biosimilar BCD-020 versus reference rituximab for treatment of patients with indolent non-Hodgkin lymphomas: An international multicenter randomized trial.
Irina V PoddubnayaSergey M AlekseevKamil D KaplanovLes M LukavetskyyGrigoriy B RekhtmanTuphan K DolaiV Satya Suresh AttiliCarlos D BermúdezAleksandr A IsaevEkaterina V ChernyaevaRoman A IvanovPublished in: Hematological oncology (2020)
BCD-020 is a proposed rituximab biosimilar, which has shown high similarity to rituximab in quality and nonclinical studies in vitro and in vivo. International multicenter clinical trial was conducted to compare efficacy and safety of BCD-020 and reference rituximab in adult (older than 18 years) patients with indolent lymphomas (follicular lymphoma grade 1-2, splenic marginal zone lymphoma, and nodal marginal zone lymphoma). Pharmacokinetics, pharmacodynamics, and immunogenicity were also studied. Patients with no previous biologic treatment for lymphoma were randomly assigned 1:1 to receive BCD-020 or comparator 375 mg/m2 for 4 weeks. Primary study outcome was day 50 overall response rate defined as complete or partial remission. Equivalence range was -20% to 20% for 95% CI for overall response rates difference. Secondary outcomes included adverse events, pharmacokinetics, pharmacodynamics, and immunogenicity. One hundred seventy-four patients were enrolled, 89 in BCD-020 arm and 85 in comparator arm. The overall response rate was 44.71% in BCD-020 arm and 41.89% in comparator arm. Limits of 95% confidence interval (CI) for difference of overall response rates between arms were (-12.62%-18.24%) showing equivalent efficacy. Sixty-one (68.54%) and 59 (69.41%) patients had at least one adverse event in BCD-020 arm or comparator arm, respectively. No unexpected adverse reactions were reported. Antidrug antibodies with no neutralizing activity were detected in two patients in comparator arm on day 14 further declining below detection threshold. Rituximab concentrations had equivalent pattern after intravenous administration of both drugs. Both drugs caused depletion of B-cells without significant influence on other blood cell lineages. In this study, we showed equivalent efficacy of BCD-020 and reference rituximab when used in patients with CD20-positive indolent lymphomas. We also confirmed pharmacokinetic equivalence of BCD-020 and reference rituximab. Safety profile, pharmacodynamics, and immunogenicity of BCD-020 were also comparable with those of reference rituximab.
Keyphrases
- diffuse large b cell lymphoma
- hodgkin lymphoma
- end stage renal disease
- clinical trial
- chronic lymphocytic leukemia
- ejection fraction
- chronic kidney disease
- newly diagnosed
- prognostic factors
- peritoneal dialysis
- randomized controlled trial
- physical activity
- squamous cell carcinoma
- patient reported outcomes
- stem cells
- low dose
- combination therapy
- bone marrow
- rheumatoid arthritis
- young adults
- replacement therapy
- rectal cancer
- single cell
- metabolic syndrome
- cell therapy
- insulin resistance
- locally advanced
- high dose
- quality improvement
- drug induced
- preterm birth