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.

Weill Cornell Lymphoma Program Study on Mantle Cell Lymphoma Has Received a Top 10 Clinical Research Forum Achievement Award from a National Clinical Research Organization

Dr. Jia Ruan examines study participant Russell Meyer. Photo credit: Carlos Rene Perez

Dr. Jia Ruan, lead author of the New England Journal of Medicine  study “Lenalidomide plus Rituximab as Initial Treatment for Mantle-Cell Lymphoma,” was in Washington on April 12 at the Clinical Research Forum fifth annual awards ceremony to receive the Top 10 Clinical Research Achievements Award.  She also presented the study at the opening plenary session during the 2016 Translational Science meeting.

The 10 winning papers were chosen based on their degree of innovation from a pool of more than 40 nominations from 30 research and academic health centers nationwide.

The multi-center phase 2 study showed that a combination therapy lacking many of the typical debilitating effects of traditional cancer treatment could effectively manage mantle cell lymphoma by inducing remissions in the vast majority of patients.

Mantle cell lymphoma (MCL) is a subtype of non-Hodgkin lymphoma that primarily affects elderly individuals. Initial treatment is not standardized and variable, but usually includes chemotherapy regimens that are generally not curative and may not be tolerated by all patients.

In this ongoing study, treatment with biologic combination of lenalidomide and rituximab led to high response rates and durable remissions in patients with previously untreated MCL, providing an effective alternative to conventional chemotherapy for a broad range of patients.

Thirty-eight patients have been treated on the study with induction and maintenance therapy. Among 36 evaluable patients, 92% responded to treatment, 64% of whom achieved complete response. Eighty-five percent of patients have no evidence of disease progression, and 97% remain alive at the two-year mark. The majority of patients reported a high quality of life as measured by quality-of-life instruments throughout treatment. The most common side effect were asymptomatic low white blood cell counts and transient inflammatory symptoms generally reversible with lenalidomide dose adjustment and supportive care.

“With this frontline treatment, we were able to achieve a very high quality and durable response rate without needing to use chemotherapy,” Ruan said. “It’s very meaningful for the patients who have always been told that their disease is without a cure.”

She thanked all of the patients who participated in the trial, as well as her Weill Cornell Medicine co-investigators: John Leonard M.D., Peter Martin M.D., Morton Coleman M.D., Richard Furman M.D., Paul Christos Dr.P.H. M.S., Orel Katz P.A., Jessica Katz P.A., and Amelyn Rodriguez R.N. Additional collaborators included Dr. Bijal Shah from Moffit Cancer Center, Drs. Steven Schuster and Jakub Svoboda from the University of Pennsylvania Abramson Cancer Center, and Dr. Sonali Smith from the University of Chicago Medical Center.

 

New Clinical Trial: Alisertib (MLN8237) or Investigator’s Choice for Relapsed/Refractory Peripheral T-Cell Lymphoma

A Phase 3, Randomized, Two-Arm, Open-Label, Multicenter, International Trial of Alisertib (MLN8237) or Investigator’s Choice (Selected Single Agent) in Patients with Relapsed or Refractory Peripheral T-Cell Lymphoma

Update: this study is closed to enrollment. 

The Weill Cornell Lymphoma Program has recently opened a new clinical trial for people with relapsed or refractory Peripheral T-Cell Lymphoma (PTCL). The sponsor is Millennium Pharmaceuticals, and the principal investigator at Weill Cornell is Dr. Jia Ruan. For more information about the study, please call Amelyn Rodgriguez, RN at (212) 746-1362 or e-mail Amelyn at amr2017@med.cornell.edu.

Study Details

The purpose of the study is to assess how well people with PTCL respond to treatment with the experimental drug Alisertib (also known as MLN8237) as compared to other PTCL treatments.

Study participants will be randomly assigned to receive Alisertib or one of the following drugs used to treat PTCL: pralatrexate, romidepsin or gemcitabine.

Alisertib has been developed to interfere with cell division, which is required for normal and cancer cell growth. By blocking an enzyme that cells need to reproduce, alistertib may slow the growth of cancer cells.

Key Eligibility

  • PTCL relapsed or refractory to at least 1 prior systemic, cytoxic therapy for PTCL
  • Must have received convential therapy (not experimental) as prior therapy

Treatment Plan

Study participants will be randomly assigned to one of two study arms:

  • Arm A: Alisertib tablet twice daily by mouth for 7 consecutive days (Cycle Days 1-7) in a 21-day cycle for up to 32 cycles of treatment (2 years)
  • Arm B: Single-arm comparator. Participants will be assigned by the investigator to receive 1 of the following for up to 2 years:
    • Pralatrexate via infusion once weekly for 6 weeks in 7-week cycles. Cycles repeated every 7 weeks
    • Romidepsin via infusion on Days 1, 8 and 15 of a 28-day cycle. Cycles repeated every 28 days
    • Gemcitabine via infusion on Days 1, 8 and 15 of a 28-day cycle. Cycles repeated every 28 days