OncLive State of the Science Summit

We’re proud to share that Dr. Peter Martin and Dr. John Leonard are co-hosting a State of the Science Summit on Hematologic Malignancies with OncLive in Queens on May 4, 2017.

This free event will feature educational sessions and a dinner and networking reception. All healthcare practitioners are welcome. Seats are limited, so register today: http://ow.ly/dfIx308iTis

OncLive State of the Science Agenda_Flyer

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 Immunotherapy Treatment Approved for Children and Adults with Hodgkin Lymphoma

On March 14, 2017, the Food and Drug Administration (FDA) approved pembrolizumab for the treatment of refractory Hodgkin lymphoma in children and adults who have been treated with at least three prior therapies.

Pembrolizumab is a type of immunotherapy called a checkpoint inhibitor. This drug consists of an antibody that binds to programmed death receptor-1 (PD-1), preventing the cancer cells from evading detection by the body’s immune system. Treatment with pembrolizumab allows T-cells (the fighter cells) to mount an immune response against the malignant cells.

Since 2014, Pembrolizumab has been FDA approved for the treatment of unresectable or metastatic melanoma, metastatic non-small-cell lung cancer, and recurrent or metastatic head and neck squamous cell carcinoma. The approval of pembrolizumab for the treatment of relapsed Hodgkin lymphoma was made under the FDA’s accelerated approval process.

This approval was based on data from a clinical trial of pembrolizumab in 210 adult patients with Hodgkin lymphoma who had relapsed or refractory disease after autologous stem cell transplant and/or treatment with brentuximab vedotin.  With a median follow up of 9.4 months, the overall response rate was 69%, including partial responses in 47% and complete responses in 22% of patients. The approval in pediatrics was based on known safety data and extrapolated efficacy based on the adult trial.

The most common adverse events in the trial were fatigue, fever, cough, musculoskeletal pain, diarrhea, and rash. Among 40 pediatric patients with advanced melanoma, PD-L1 positive tumors, or lymphoma, the side effects and overall safety profile was similar to adults.  A “warning and precaution” was added to the label describing the potential complications of graft-versus-host disease (GVHD) in patients undergoing allogeneic stem cell transplant after treatment with pembrolizumab.  Death related to GVHD has occurred and physicians are advised to monitor for hepatic veno-occlusive disease and grade 3-4 acute GVHD including hyperacute GVHD.

The recommended dose of pembrolizumab for patients with Hodgkin lymphoma is 200mg every 3 weeks in adults and 2mg/kg (up to 200mg) every 3 weeks in children.

At the Weill Cornell and NewYork-Presbyterian Lymphoma Program, we offer pembrolizumab as one of many treatment choices available for people with Hodgkin lymphoma.