The Impact of Rituximab on the Clinical Outcomes of Primary Central Nervous System Lymphoma (PCNSL) When Added to Combination Chemotherapy: A Comprehensive Meta-Analysis

Introduction:

PCNSL is a rare diffuse large B-cell lymphoma (DLBCL) confined to the central nervous system accounting for approximately 2-5% of all primary brain tumors. Although there is no standard combination of chemotherapy, high-dose methotrexate is considered the backbone of all PCNSL chemotherapy regimens. Rituximab, an anti-CD20 antibody, has been a standard component of non-CNS DLBCL combinations since it improves progression-free (PFS) and overall survival (OS). However, the role of Rituximab in the treatment of PCNSL has been controversial with contradictory results. A meta-analysis conducted in 2019 found no associated survival advantage for Rituximab when added to chemotherapy. However, this meta-analysis was small and included only 2 studies. The purpose of this meta-analysis is to evaluate in a more comprehensive way the impact of Rituximab-based chemotherapy combinations on the clinical outcomes of patients with PCNSL incorporating all available comparative studies.

Methods:

A review of the medical literature was conducted using online databases. Inclusion criteria consisted of PCNSL diagnosis, English language, and studies reporting OS and PFS with hazard ratios (HR) or Kaplan-Meier curves that compared similar regimens with and without Rituximab. A meta-analysis using an inverse variance method with a random-effects model was conducted.

Results:

Four comparative studies with a total of 467 patients were included in this meta-analysis. Two of these studies were retrospective comparative studies and two were randomized phase II trials. When added to chemotherapy, Rituximab was found to significantly improve the OS and PFS (HR_OS 0.75, 95%CI: 0.59-0.96, p=0.02; HR_PFS 0.67, 95%CI: 0.53-0.85, p=0.001) with a heterogeneity estimate, I²=0%.

Conclusions: This is the first meta-analysis to show that adding Rituximab to chemotherapy is associated with OS and PFS in patients with PCNSL. In the absence of randomized clinical trials, this meta-analysis represents the most compelling data supporting the routine use of Rituximab combinations in PCNSL.