Chemo-Free Follicular Lymphoma Treatment Regimen Shows Promise in Phase II Clinical Trial

CaptureThe combination of lenalidomide and rituximab may represent a reasonable alternative to chemotherapy for some people with previously untreated follicular lymphoma (FL), according to a study led by Dr. Peter Martin, chief of the Weill Cornell Medicine and NewYork-Presbyterian Hospital (WCM/NYP) Lymphoma Program.

Dr. Martin collaborated with the Lymphoma Program’s Drs. Jia Ruan and John Leonard, along with experts from academic medical centers across the country, to evaluate the non-chemotherapy drug combination in a phase II trial known as CALGB 50803, the results of which were recently published in the Annals of Oncology. The formalized collaboration was made possible by the Alliance for Clinical Trials in Oncology, a cooperative group sponsored by the National Cancer Institute (NCI).

Lenalidomide plus rituximab was administered over twelve 28-day cycles to 65 adults with previously untreated follicular lymphoma. Seventy-two percent of patients achieved a complete response. At five years, the overall survival rate was 100 percent, and 70 percent of patients remained free from disease progression. Rates are comparable with those typically produced by standard chemotherapy.

The study also demonstrated low rates of hematologic toxicity, such as neutropenia (low white blood cell count), lymphopenia (low lymphocyte levels) and thrombocytopenia (low platelet count), but low-grade side effects like fatigue, constipation, diarrhea and rash were commonly reported.

The results of the CALGB 50803 study do not definitively establish whether lenalidomide-rituximab is more or less toxic or more or less effective than a standard chemotherapy regimen; such insights will be clearer following completion of the randomized phase III RELEVANCE trial, which compares lenalidomide-rituximab to chemotherapy plus rituximab.

Optimal use of chemotherapy requires a careful balance of anti-tumor activity with tolerability. WCM/NYP is proud to be a leader in the discovery and development of therapies that are both active against cancer and well tolerated.

FDA Approves Subcutaneous Administration of Rituximab for Three Lymphoma Types

On June 22, 2017, the United States Food and Drug Administration (FDA) approved subcutaneous injection of rituximab plus hyaluronidase human for people with follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), and chronic lymphocytic leukemia (CLL). Subcutaneous administration refers to the method of delivering a drug under the skin rather than directly into a vein as performed during intravenous (IV) administration.

insulin injection

Administration of rituximab under the skin tends to take less than 10 minutes, whereas the traditional IV method can last several hours. The technique also allows for fixed dosing, which can reduce preparation time and excess drug waste, and may be more cost effective than IV infusion.

The approved treatment is to be employed only after patients have received at least one cycle of intravenous rituximab.

Approval comes based on the results of a series of clinical trials demonstrating comparable safety and efficacy outcomes across subcutaneous and intravenous administration.

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.