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 Dose-Escalation Study of the Safety and Pharmacokinetics of LAM-002A Administered Orally in Subjects with Relapsed or Refractory B-cell non-Hodgkin Lymphoma

The Weill Cornell Medicine Lymphoma Program has recently opened a new clinical trial for men and women with previously-treated B-cell non-Hodgkin lymphoma. (B-cell NHL) The study sponsor is LAM Therapeutics, 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

Study Summary

This clinical trial is for men and women with B-cell non-Hodgkin lymphoma (B-cell NHL) who were previously treated for this disease.

Management of patients with non-Hodgkin lymphoma varies widely depending on histology. Patients with DLBCL who relapse after, or who are not candidates for ASCT, as well as patients with relapsed mantle cell lymphoma, marginal zone lymphoma, follicular lymphoma, and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) are not considered curative with conventional therapies. Therefore management of relapsed and refractory NHL remains an unmet medical need.

This is a Phase 1, single-arm, open-label dose-escalation study of the safety and pharmacokinetics of LAM-002A administered orally in subjects with relapsed or refractory B-cell NHL. There will be a dose-escalation stage and an expansion stage for this study. The study drug will be administered on a twice daily oral dosing regimen with a cycle length of 28 days. Patients will continue on treatment as long as they are responding to therapy and not experiencing unacceptable side effects. All patients will be followed for overall survival every three months via telephone contact during the post-treatment follow-up period.

Key Eligibility

  • Men and women age 18 and older with histologically confirmed diagnosis of B-cell NHL limited to follicular lymphoma, DLBCL, mantle cell lymphoma, marginal zone lymphoma, or CLL/SLL.
  • Prior therapy must have included a rituximab-based chemo-immunotherapy regimen.
  • Detailed eligibility reviewed when you contact the study team.
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