On June 22, 2017, the U.S. Food and Drug Administration (FDA) approved a new drug for the treatment of follicular lymphoma (FL), diffuse large B-cell lymphoma (diffuse large B-cell lymphoma (DLBCL), and chronic lymphocytic leukemia (CLL) – a combination therapy of rituximab in combination with hyaluronidase (trade name Rituxan Hycela, manufactured by Sunbase).
This drug is administered by subcutaneous injection for the treatment of patients with:
- monotherapy for relapsed or refractory follicular lymphoma;
- For primary follicular lymphoma, in combination with first-line chemotherapy, as single-agent maintenance therapy in patients who have achieved complete or partial remission with rituximab in combination with chemotherapy;
- For follicular lymphoma without disease progression (stable disease), as monotherapy after the standard treatment CVP regimen (cyclophosphamide, vincristine, and prednisone);
- for primary treatment of diffuse large B-cell lymphoma, in combination with a CHOP regimen (cyclophosphamide, doxorubicin, vincristine, prednisone) or other anthracycline-based agents;
- for primary or treated chronic lymphocytic leukemia, in combination with an FC regimen (fludarabine, cyclophosphamide).
These indications are similar to those for which RITUXAN has been previously approved.
What is Rituxan Hycela?
Rituxan Hycela is a combination therapy of rituximab and hyaluronidase. Rituximab is a monoclonal antibody that binds to the CD20 antigen on B cells, triggering the body’s immune response against the B cells, which kills the cancer cells. The other component, hyaluronidase, increases the permeability of the subcutaneous tissues by temporarily depolymerizing hyaluronic acid to facilitate the absorption of the drug.
How rituximab works
Rituxan Hycela is a subcutaneous drug that is administered in a fixed dose over a shorter time of 5 to 7 minutes, independent of the patient’s body surface area, compared to a traditional intravenous (90 minutes) dose.
Why is Rituxan Hycela effective in follicular lymphoma, diffuse large B-cell lymphoma, and chronic lymphocytic leukemia?
- Follicular lymphoma: A B-cell lymphoma that originates from germinal center B cells and mostly forms follicle-like structures. Early-stage follicular lymphoma can be cured by involvement field radiotherapy (IF-RT), but some patients will experience relapse outside the radiotherapy area. Intermediate to advanced follicular lymphoma is treated primarily with rituximab in combination with chemotherapy.
- Diffuse large B-cell lymphoma: It is the most common type of non-Hodgkin’s lymphoma species and is divided into three main types containing three distinct molecular subtypes, including the germinal center B-cell type, the activated B-cell-like type, and the heterozygous type with no clear features. The current standard of care for diffuse large B-cell lymphoma is the RCHOP regimen (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone).
- Chronic lymphocytic leukemia: A clonally proliferative tumor of mature B lymphocytes with specific immunophenotypic features, characterized by aggregation of lymphocytes in the peripheral blood, bone marrow, spleen, and lymph nodes, occurring primarily in middle-aged and older adults.
Both follicular lymphoma, diffuse large B-cell lymphoma, and chronic lymphocytic leukemia are malignant lesions that occur in B cells, and CD20 antigen is expressed on the surface of all B cells, from pre-B cells to mature B cells. However, on the surface of other normal cells, there is no CD20 expression. rituximab in Rituxan Hycela, specifically binds CD20 antigen and, upon binding, activates complement-dependent B-cell cytotoxicity; for the human Fc receptor, mediates cell killing through antibody-dependent cytotoxicity.
Evidence of efficacy: efficacy and safety similar to rituximab
The approval of Rituxan Hycela was based on the results of several randomized clinical trials in which 410 patients with previously untreated CD20-positive follicular lymphoma received either Rituxan Hycela or rituximab in a phase III trial. At the end of treatment, the overall remission rates for the two drugs were 84.4% and 84.9%, respectively, and the incidence of serious adverse events was 37% and 34%, respectively. Phase III clinical trials in patients with diffuse large B-cell lymphoma and chronic lymphocytic leukemia also showed similar efficacy and side effects for Rituxan Hycela and rituximab.
These studies demonstrated that:
- Rituxan Hycela at a Ctrough of 1400 mg/23400 units is not inferior to intravenous rituximab at 375 mg/m;
- Rituxan Hycela at 1600 mg/26800 units of Rituximab (Ctrough) is not inferior to intravenous Rituximab at 500 mg/m;
- In multiple trials comparing Rituxan Hycela with intravenous rituximab, the efficacy and safety profile were comparable.
Black box warning: need to be alert for skin reactions, hepatitis B virus reactivation, and progressive polymorphic leukoencephalopathy
The most common adverse reactions to Rituxan Hycela include primarily infections, neutropenia, nausea, constipation, cough, and fatigue. In patients with diffuse large B-cell lymphoma, the most common adverse events observed included infection, neutropenia, alopecia, nausea, and anemia. In patients with chronic lymphocytic leukemia, the most common adverse events observed were infection, neutropenia, nausea, thrombocytopenia, fever, vomiting, and injection site erythema.
It should be noted that the instructions for Rituxan Hycela include a black box warning that the drug may cause severe and fatal skin-mucosal reactions, hepatitis B virus reactivation, and progressive multifocal white matter encephalopathy.
In addition to this, serious adverse reactions that may be caused by Rituxan Hycela include hypersensitivity reactions, tumor lysis syndrome, infections, cardiac arrhythmias, nephrotoxicity, and intestinal obstruction and perforation.
How do I use Rituxan Hycela?
According to the approved product insert, the recommended use and dosage of Rituxan Hycela is as follows:
Rituxan Hycela requires at least 1 full dose of rituximab given intravenously before initial treatment.
- For patients with chronic lymphocytic leukemia, the recommended dose is 1600 mg of rituximab and 26,800 units of hyaluronidase in 1 cycle of 28 days for 5 cycles.
- For patients with diffuse large B-cell lymphoma, the recommended dose is 1400 mg rituximab and 23,400 units of hyaluronidase in 1 cycle of 28 days for up to 7 cycles.
- For patients with follicular lymphoma, the recommended dose is 1400 mg rituximab and 23,400 units of hyaluronidase. In relapsed or refractory follicular lymphoma, once weekly for 3 to 7 weeks; in relapsed or refractory follicular lymphoma, once weekly for 3 weeks; in primary follicular lymphoma, one cycle of 21 days for 7 cycles; and in follicular lymphoma without progression after first-line therapy, once weekly for 3 weeks, with an interval of one month, with the possibility of re-dosing up to 16 doses.
Rituxan Hycela is not yet available in this country, but the subcutaneous administration of the drug makes the dosing time significantly shorter and more convenient for patients to receive treatment.