A formulation of rituximab administered by subcutaneous injection appears to be just as safe and effective in the treatment of follicular lymphoma as IV rituximab, according to a Phase III multinational trial.

Use of the subcutaneous agent, which contains the same monoclonal antibody as the IV version, could significantly reduce the amount of time patients spend in treatment visits.

“This study does give us a potential new option for these patients,” said Craig A. Portell, MD, an assistant professor of medicine at the University of Virginia, in Charlottesville. “It is equally effective and may be better tolerated. The big question is how much volume is given to the patient under the skin; large volumes can sometimes be difficult to manage.”

In the Phase III SABRINA trial, in which 113 centers from 30 countries participated, 410 patients with confirmed, previously untreated grade 1, 2 or 3a follicular lymphoma were randomly assigned to receive either 375 mg/m² of IV rituximab (Rituxan, Genentech) or 1,400 mg of subcutaneous rituximab, with 205 patients in each arm (Lancet Haematol 2017 May 2. [Epub ahead of print], PMID: 28476440). Rituximab was administered in addition to chemotherapy for eight cycles every three weeks, after which patients were maintained on rituximab every eight weeks. The primary end point was overall response.

At the end of induction, the researchers found an overall response in 84.9% of patients who received IV rituximab, and in 84.4% of those who received the agent subcutaneously.

Adverse events (AEs) occurred at a nearly identical rate: in 199 (95%) patients in the IV group and 197 (96%) in the subcutaneous group. Grade 3 AEs, the most common of which was neutropenia, also occurred at a similar rate: in 116 (55%) patients in the IV group and 11 (56%) in the subcutaneous group. Serious AEs affected 72 (34%) and 73 (37%) patients in the IV and subcutaneous arms, respectively.

The biggest difference was in the rate of administration-related reactions, mainly injection site reactions, which were documented in 73 (35%) patients in the IV arm and 95 (48%) in the subcutaneous arm.

The availability of subcutaneous rituximab may have the potential to change practice; IV administration of the agent takes at least 90 minutes and can require up to six hours. Subcutaneous rituximab administration can take between five and seven minutes.

“Certainly less time in the infusion chair is a potential benefit for patients, both financially and timewise,” Dr. Portell said.

It also might have an effect on the distribution of resources. “We wouldn’t need as many nurses in the infusion center to administer subcutaneous injections. But the impact on resources would depend on whether patients would need to be monitored for long after the injection,” Dr. Portell said. “I imagine that after a while patients wouldn’t need to be monitored, but it’s hard to know that from what’s been published so far.”

Subcutaneous administration may not be ideal for all patients, especially those who have skin problems, he pointed out. “People with eczema, psoriasis or other allergic skin reactions may find this hard to manage. So would patients with thin skin—some of our elderly individuals have a hard time tolerating large subcutaneous injections.”

Dr. Portell speculated that blood thinners may affect tolerance, “but I imagine this wouldn’t be too much of a problem, depending on the volume that is injected.”

Subcutaneous rituximab has been used in Europe since 2014 and has been approved in about 50 countries around the world. In a unanimous, 11-0 vote in late March, the FDA’s Oncologic Drugs Advisory Committee deemed the subcutaneous formulation as favorable for follicular lymphoma as well as large B-cell lymphoma and refractory chronic lymphocytic leukemia. A decision on approval is expected from the FDA by June 26, 2017.

—Monica J. Smith

Dr. Portell reported a financial relationship with Genentech.