High-dose methotrexate-based regimens and post-remission consolidation for treatment of newly diagnosed primary CNS lymphoma: meta-analysis of clinical trials

Abstract

With the exception of high-dose methotrexate (HD-MTX), there is currently no defined standard treatment for newly diagnosed primary central nervous system lymphoma (PCNSL). This review focused on first-line induction and consolidation treatment of PCNSL and aimed to determine the optimal combination of HD-MTX and the long-term beneficial consolidation methods. A comprehensive literature search of MEDLINE identified 1407 studies, among which 31 studies met the inclusion criteria. The meta-analysis was performed by using Stata SE version 15. Forest plots were generated to report combined outcomes like the complete response rate (CRR), overall survival, and progression-free survival. We also conducted univariate regression analyses of the baseline characteristics to identify the source of heterogeneity. Pooled analysis showed a CRR of 41% across all HD-MTX-based regimens, and three- and four-drug regimens had better CRRs than HD-MTX monotherapy. In all combinations based on HD-MTX, the HD-MTX + procarbazine + vincristine (MPV) regimen showed pooled CRRs of 63% and 58% with and without rituximab, respectively, followed by the rituximab + HD-MTX + temozolomide regimen, which showed a pooled CRR of 60%. Pooled PFS and OS showed that post-remission consolidation with autologous stem cell transplantation (ASCT) was associated with the best survival outcome, with a pooled 2-year OS of 80%, a 2-year PFS of 74%, a 5-year OS of 77%, and a 5-year PFS of 63%. Next, whole-brain radiation therapy (WBRT) + chemotherapy showed a pooled 2-year OS of 72%, 2-year PFS of 56%, 5-year OS of 55%, and 5-year PFS of 41%, with no detectable CR heterogeneity throughout the entire treatment process. In HD-MTX-based therapy of newly diagnosed PCNSL, MPV with or without rituximab can be chosen as the inductive regimen, and the rituximab + HD-MTX + temozolomide regimen is also a practical choice. Based on our study, high-dose chemotherapy supported by ASCT is an efficacious approach for consolidation. Consolidation with WBRT + chemotherapy can be another feasible approach.

Primary Central Nervous System Lymphoma: Focus on Indian Perspective

“…Only marginally better are conventional DLBCL regimes with response rates ranging from 19 to 59% and less than half patients surviving at two years from diagnosis [2,3]. A significant improvement in prognosis comes from modern multidrug regimens incorporating high-dose methotrexate (HD-MTX) with appropriate consolidation (2 years OS of 80% and a five-year OS of 77%) [47]. More recent regimes utilizing autologous stem cell transplantation as consolidation report twoyear OS as high as 81% [48].…”

Advances in treatment of elderly primary central nervous system lymphoma

“…Combination of HD‐MTX with other cytostatic agents provides best clinical results, when feasible. Two meta‐analyses have demonstrated HD‐MTX in combination with other agents (particularly cytarabine) is associated with highest response rates and improved survival outcomes 51 . The use of rituximab in PCNSL has been a matter of recent controversy; the phase 3 Hovon 105/ALLG‐NHL‐24 trial found no benefit of rituximab addition to the MTX/carmustune/teniposide/prednisone combination (MBVP).…”

Recent Progress on Primary Central Nervous System Lymphoma—From Bench to Bedside

“…Generally, PCNSL has a cure rate below 40% with MTX-based regimens and is subject to late recurrences (1,(29)(30)(31)(32). In their analysis of 31 studies published between 1992 and 2019, Yu et al have reported that PCNSL patients achieved a pooled CRR of 41% across all HD-MTX-based regimens (33). Additionally, three-and four-drug regimens achieved better CRRs than HD-MTX monotherapy (33).…”