Subcutaneous Rituximab: Coming Soon?

Paola Ghione, MD

Dr. Ghione is a visiting hematology fellow from Torino, Italy who is working with the Weill Cornell Lymphoma Program for six months.

Rituximab is a drug that is used to treat B-cell non-Hodgkin lymphomas. It is a type of immunotherapy called a monoclonal antibody, and it works by targeting CD20, a protein present on the surface of the B-cells.

insulin injectionIn the United States, rituximab is administered by intravenous (IV) infusion, often over several hours. In March 2014, a formulation of rituximab for subcutaneous injection (under the skin rather than directly into the vein) was approved by the European Medicines Agency, and Health Canada approved the subcutaneous formulation in September 2016. At my home institution – the University of Torino — we have been using subcutaneous rituximab routinely. Advantages for patients include the faster administration time, usually less than 10 minutes. Institutions may prefer subcutaneous rituximab because it is administered as a fixed dose, which can reduce the preparation time and waste.

The first study to compare the two formulations was conducted in Europe from 2009 to 2012 in 124 people receiving rituximab maintenance for follicular lymphoma. The purpose of this study was to identify a comparable dose and to compare safety. The second study, called “SABRINA” was conducted in Europe, Canada, and Thailand, with the participation of 127 people with previously untreated follicular lymphoma who were receiving chemotherapy plus rituximab. Patients responded equally to treatment with both formulations (intravenous versus subcutaneous), and no differences were found in terms of safety. In comparing the side effects, IV administration was linked to more gastrointestinal-based events (such as diarrhea and nausea), while skin reactions (usually redness at the injection site) were more common with subcutaneous rituximab.

In another large study, called “MABEASE,” 576 people with diffuse large B-cell lymphoma participated in a clinical trial in which they were randomized to receive CHOP chemotherapy with either subcutaneous or intravenous rituximab. Again, the efficacy of the two formulations was similar and the subcutaneous administration was associated with increased administration-related reactions (mainly rash).

Finally, a clinical trial called “PrefMab” enrolled more than 700 people with diffuse large B-cell lymphoma and follicular lymphoma with the aim of evaluating patient satisfaction using both administration methods. One group of participants started with intravenous infusion and then switched to subcutaneous, and vice-versa for the second group. In general, patients preferred the subcutaneous formulation. Specifically, 80% of the patients preferred the subcutaneous formulation, 10% still preferred the intravenous one and 10% had no preference. This preference was largely due to the reduction of time spent in the hospital and the comfort of the administration.

In addition to efficacy, safety, and patient preference, the financial impact of the new formulation is worth considering. Two groups have conducted economic studies on this subject. The Roche study found that the subcutaneous formulation was associated with reduced costs due to less staff time (nurses, technicians and pharmacists), shorter time in the bed/chair in the infusion center, and a reduction in wasted drug and materials related to the infusion. The Italian study reported an overall saving of 6.057 euros ($6.464 USD) for each rituximab administration. The financial impact might differ in different healthcare systems.

Subcutaneous rituximab is not currently available in the United States, but the Food and Drug Administration (FDA) accepted a Biologics License Application in November 2016. This means that probably the formulation will be soon available in the U.S. market.

New Clinical Trial: A Phase 1 Study to Assess Safety/Tolerability of REGN1979 & REGN2810 in Patients with B-Cell Malignancies

The Weill Cornell Medicine Lymphoma Program has recently opened a new clinical trial for men and women with B-cell non-Hodgkin lymphoma. The study sponsor is Regeneron Pharmaceuticals, Inc., and the principal investigator at Weill Cornell is Sarah Rutherford, M.D. For more information about the study, please call Rita Gazivoda, RN at 212-746-0702 or e-mail Rita at rig9021@med.cornell.edu.

Key Eligibility

  • Men and women age 18 and older with either B-cell non-Hodgkin lymphoma with active disease that is either refractory to or relapsed after most recent prior therapy for whom no standard of care options exist or documented Hodgkin lymphoma with active disease not responsive to prior therapy or relapsed after prior therapy for whom no standard of care options exist.
  • Detailed eligibility reviewed when you contact the study team.

Study Summary

This clinical trial is for men and women with lymphoma for whom no standard of care options exist. Currently available treatments for lymphoma are effective in some patients, however, other patients experience relapse or refractory disease following treatment. Therefore, there is a need to find more effective treatments when patients fail to respond to existing standard of care options. Patients will be administered REGN2810 intravenously every 2 weeks at a specified dose level. Patients will receive REGN2810 for a minimum of 12 doses (24 weeks) and up to a maximum of 24 doses (48 weeks). Upon completion of treatment, there will be a 24-week follow-up period. Patients will continue on treatment as long as they are responding to therapy and not experiencing unacceptable side effects.

Dr. John Leonard Discusses Chimeric Antigen Receptor (CAR) T-cell Therapy for Patients with Advanced B-Cell Lymphoma

In an article from Healio HemOnc Today, Lymphoma Program Director Dr. John Leonard commented on a study presented at the 2016 ASCO meeting, which reported that for patients with advanced B-cell lymphoma, remission could be induced through a combination of low-dose chemotherapy and genetically modified T-cells. These genetically modified T-cells are known as chimeric antigen receptor (CAR) T-cells. They are modified to specifically target the CD-19 proteins found on the surface of B-cells. On the findings of the study he said,

“These represent additional data that show that this treatment regimen has potential in the treatment of patients with resistant, aggressive lymphoma. As far as follow-up is concerned, we need additional studies with larger groups of patients, with longer follow-up periods, to see if these responses are going to be durable.”

Look to this space for additional information on CAR T-cell therapy at Weill Cornell Medicine.