In the Clinic provides overviews of novel oncology agents, addressing indications, mechanisms of action, administration recommendations, safety profiles, and other essential information needed for the appropriate clinical use of these drugs.

Late in 2018, rituximab-abbs was approved as the first biosimilar to rituximab for adult patients with CD20-positive, B-cell non-Hodgkin lymphoma (NHL) to be used as a single agent or in combination with chemotherapy.^1,2

Rituximab-abbs is indicated for the treatment of adult patients with:

• Relapsed or refractory, low-grade or follicular, CD20-positive, B-cell NHL as a single agent
• Previously untreated follicular, CD20-positive, B-cell NHL in combination with first-line chemotherapy and, in patients achieving a complete or partial response to a rituximab product in combination with chemotherapy, as single-agent maintenance therapy
• Nonprogressing (including stable disease), low-grade, CD20-positive, B-cell NHL as a single agent after first-line cyclophosphamide, vincristine, and prednisone (CVP) chemotherapy.²

Health-care professionals should review product labeling for detailed information on the use of rituximab-abbs. Rituximab-abbs should be administered only by a health-care professional with appropriate medical support to manage severe infusion reactions that can be fatal.

Approval Process

The approval was based on comparisons of extensive structural and functional product characterization, animal data, human pharmacokinetic and pharmacodynamic data, clinical immunogenicity, and other clinical safety and effectiveness data demonstrating that rituximab-abbs is biosimilar to U.S. rituximab.

Rituximab-abbs has been approved as a biosimilar, not as an interchangeable product. As defined by the U.S. Food and Drug Administration (FDA), a biosimilar “is a biological product that is highly similar to and has no clinically meaningful differences from an existing FDA-approved reference product.”

To satisfy the criteria of having no clinically meaningful differences, a manufacturer of a biosimilar product must demonstrate the absence of such differences from the reference product in terms of safety, purity, and potency (safety and effectiveness); this is generally demonstrated through human pharmacokinetic and pharmacodynamic studies, an assessment of clinical immunogenicity, and, if needed, additional clinical studies.

As stated by the FDA: “An interchangeable product is a biosimilar product that meets additional requirements outlined by the Biologics Price Competition and Innovation Act. As part of fulfilling these additional requirements, information is needed to show that an interchangeable product is expected to produce the same clinical result as the reference product in any given patient. Also, for products administered to a patient more than once, the risk in terms of safety and reduced efficacy of switching back and forth between an interchangeable product and a reference product will have been evaluated.” An interchangeable product may be substituted for a reference product without the involvement of the prescriber.

Recommended Dosing in NHL

The recommended dose of rituximab-abbs is 375 mg/m² as an intravenous infusion according to the following schedules:

• Relapsed or refractory, low-grade or follicular, CD20-positive, B-cell NHL: Administer once weekly for four doses.
• Retreatment for relapsed or refractory, low-grade or follicular, CD20-positive, B-cell NHL: Administer once weekly for four doses.
• Previously untreated, follicular, CD20-positive, B-cell NHL: Administer on day 1 of each cycle of chemotherapy for up to eight doses. In patients with a complete or partial response, initiate rituximab-abbs maintenance 8 weeks after completion of a rituximab product in combination with chemotherapy. Administer rituximab-abbs as a single agent every 8 weeks for 12 doses.
• Nonprogressing, low-grade, CD20-positive, B-cell NHL after first-line CVP chemotherapy: After completion of front-line chemotherapy, administer once weekly for 4 doses at 6-month intervals, to a maximum of 16 doses.

Safety

As with rituximab, rituximab-abbs has boxed warnings for fatal infusion reactions within 24 hours of infusion; severe mucocutaneous reactions, some with fatal outcomes; hepatitis B virus reactivation, in some cases resulting in fulminant hepatitis, hepatic failure, and death; and progressive multifocal leukoencephalopathy resulting in death.

As with rituximab, rituximab-abbs also has warnings/precautions for tumor-lysis syndrome, infections, cardiac adverse reactions, renal toxicity, bowel obstruction and perforation, immunizations, and embryofetal toxicity. Patients should be advised not to breastfeed while receiving rituximab-abbs. 

REFERENCES

1. U.S. Food and Drug Administration: FDA approves Truxima as biosimilar to Rituxan for non-Hodgkin’s lymphoma. Available at www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm627035.htm. Accessed December 10, 2019.

2. Truxima (rituximab-abbs) injection prescribing information, Celltrion Inc, November 2018. Available at www.accessdata.fda.gov/drugsatfda_docs/­label/2018/761088s000lbl.pdf. Accessed December 10, 2019.