Bromberg JEC, et al. - In patients with newly diagnosed primary CNS lymphoma, researchers investigated whether the addition of rituximab (a chimeric monoclonal antibody that targets the CD20 cell surface protein) to a high-dose methotrexate-based chemotherapy regimen offers any benefit. They found that the addition of rituximab to methotrexate, carmustine, teniposide, and prednisone chemotherapy did not offer any clear benefit in primary CNS lymphoma; rituximab should not be a component of standard treatment in primary CNS lymphoma.

Methods

• In the Netherlands, Australia, and New Zealand, researchers conducted this intergroup, multicenter, open-label, randomized phase 3 study at 23 hospitals.
• Participants were non-immunocompromised patients aged 18-70 years with newly diagnosed primary CNS lymphoma.
• Through random assignment (1:1), participants were administered methotrexate-based chemotherapy with or without intravenous rituximab.
• A web-based randomization system with stratification by center, age, and Eastern Cooperative Oncology Group–WHO performance status, and a minimization procedure, was used.
• Open label assignment was used for all group assignment and neither investigators nor patients were masked to allocation.
• All patients were treated with two 28-day cycles of induction chemotherapy, consisting of intravenous methotrexate 3 g per m² on days 1 and 15, intravenous carmustine 100 mg per m² on day 4, intravenous teniposide 100 mg per m² on days 2 and 3, and oral prednisone 60 mg per m² on days 1–5, with (R-MBVP) or without (MBVP) intravenous rituximab 375 mg per m² on days 0, 7, 14, and 21 in cycle one and days 0 and 14 in cycle two.
• At the end of induction, those who exhibited response were administered high-dose cytarabine; low-dose whole-brain radiotherapy was used in those aged 60 years or younger.
• Using analysis adjusted for age and performance score, they assessed event-free survival (primary endpoint), with events defined as not reaching complete response or complete response unconfirmed at the end of treatment, or progression or death after response.
• They analyzed patients on a modified intention-to-treat basis.

Results

• This study included 200 patients (109 men and 91 women; median age was 61 years [IQR 55–67]) recruited between August 3, 2010 and May 27, 2016.
• Randomly, MBVP was given to 100 patients and R-MBVP to 99 patients.
• One patient was excluded from all analyses, although was randomly assigned to the R-MBVP group; the reason for exclusion was ineligibility due to an incorrect diagnosis.
• An event occurred (51 in the MBVP group and 47 in the R-MBVP group) in 98 patients, after a median follow-up of 32.9 months (IQR 23.9–51.5), and death was reported in 79 cases among these patients (41 in the MBVP group and 38 in the R-MBVP group).
• In the MBVP group and in the R-MBVP group (hazard ratio 1.00, 95% CI 0.70–1.43, p=0.99), the event-free survival at 1 year was 49% (95% CI 39–58) and 52% (42–61), respectively.
• In the MBVP group and in the R-MBVP group, grade 3 or 4 adverse events were observed in 58 (58%) patients and 63 (64%) patients, respectively.
• The most common grade 3 or 4 adverse events documented in this study included infections (24 [24%] patients receiving MBVP vs 21 [21%] patients receiving R-MBVP), hematological toxicity (15 [15%] vs 12 [12%]), and nervous system disorders (ten [10%] vs 15 [15%]).
• Twelve (12%) patients in the MBVP group and ten (10%) patients in the R-MBVP group experienced life-threatening or fatal serious adverse events.
• Death attributed to treatment-related causes was reported in 5 (5%) patients in the MBVP group and 3 (3%) in the R-MBVP group.