Adding Rituxan (rituximab) to standard first-line chemotherapy did not improve disease outcomes for people with primary central nervous system (CNS) lymphoma in a Phase 3 clinical trial, results show.
Primary CNS lymphoma is a rare type of non-Hodgkin’s lymphoma that occurs in the brain. Patients are usually treated with high-dose methotrexate-based chemotherapy, with or without radiation therapy to the brain, but prognosis remains very poor.
Most CNS lymphomas are diffuse large B-cell lymphomas, whose cells are positive for the CD20 factor. These lymphomas, when outside the brain, respond fairly well to the CD20 antibody Rituxan. But those in the brain face the challenges of any brain tumor, particularly when it comes to the blood-brain barrier limiting or preventing a treatment from reaching its target.
While Rituxan is among the molecules that cannot enter the brain under normal circumstances, studies suggest that both lymphoma cells and chemotherapy disrupt this barrier, allowing Rituxan to enter for a short period of time.
To test this hypothesis, researchers designed a Phase 3 trial (NTR2427) studying if a combination of Rituxan and standard chemotherapy — methotrexate, carmustine, teniposide and prednisone — would extend the time patients lived without an “event.”
“We defined an event as the absence of complete response or unconfirmed complete response at the end of all protocol treatment, or relapse or death after previous complete response or unconfirmed complete response,” they wrote.
The study included 199 patients, median age of 61, with newly diagnosed disease and enrolled at hospitals in the Netherlands, Australia, and New Zealand. They were randomly assigned Rituxan plus chemotherapy, or chemotherapy alone. Approximately one-third of patients in each group also received radiation therapy to the brain.
After a median follow-up of 32.9 months, 98 patients had experienced an event and 79 had died.
Outcomes were similar among the two treatment groups, with 52% of those on Rituxan having an event at one year, versus 49% for those on chemotherapy only. The proportion of patients alive and progression-free at one year was also similar between these groups — 65% versus 58% – as was the proportion of responders, 86% for both groups.
Survival rates were not statistically different at one, two, and three years.
The treatment was as safe as chemotherapy, with a similar proportion of patients experiencing serious side effects. The most common were infections, blood toxicity, and nervous system disorders. Eight deaths were deemed treatment-related; five in the chemotherapy group and three in the Rituxan group.
“In this randomised phase 3 study, we found that adding rituximab to standard MBVP chemotherapy did not improve event-free survival, overall survival, or progression-free survival in patients with newly diagnosed primary CNS lymphoma compared with MBVP alone,” the researchers wrote.
These findings contrasted with those of a Phase 2 trial conducted during the same period. However, its “results might be caused by chance effects because the study was not designed for comparison,” the investigators said.