Outcomes of older patients with primary central nervous system lymphoma treated in routine clinical practice in the UK: methotrexate dose intensity correlates with response and survival

Abstract

Summary Data on older patients with primary central nervous system lymphoma (PCNSL) are scarce. Comorbidities and performance status frequently compromise outcomes in this group. Medical records for consecutive patients ≥65 years (n = 244) with PCNSL diagnosed 2012–2017 from 14 UK centres were retrospectively reviewed. Of these 192 patients received methotrexate (MTX)‐based treatment. Patients were categorised based on clinician's treatment choice into ‘palliative’ (n = 52), ‘less intensive: MTX ± rituximab ± alkylators’ (n = 74) and ‘intensive: MTX/cytarabine combinations’ (n = 118) groups. Complete remission (CR) rate, two‐year progression‐free survival (PFS) and overall survival (OS) rates were 49%, 11% and 24% for the less intensive and 69%, 40% and 50% for the intensive groups. Treatment‐related mortality (TRM) was 6·8% for MTX‐treated patients. Median MTX cumulative dose was 8·8 g/m2 (range 1·5–21) over a median of three cycles. Higher relative dose intensity of MTX (MTX‐RDI) was associated with improved PFS and OS in both groups adjusting for age, Eastern cooperative oncology group (ECOG) score and baseline parameters. Two‐year PFS and OS for patients receiving four or more induction cycles followed by consolidation (n = 36) were 65% and 70% respectively. Older patients completing MTX‐based induction and consolidation had clinical outcomes similar to those in younger cohorts. These retrospective data suggest that maximising MTX‐RDI and delivering consolidation in a subgroup of older patients may improve clinical outcomes.

Treatment patterns and disease course of previously untreated Primary Central Nervous System Lymphoma: Feasibility of MTX‐based regimens in clinical routine

“…Still, treatment of these patients with MTX‐based regimens in clinical routine seems to be feasible and results in favorable outcomes in a relevant proportion of these patients. In fact, another report suggests that higher dose intensity of MTX is a major contributor to favorable outcomes 28 . Patients receiving a median amount of 10,6 g/m 2 MTX showed two‐year overall survival of 50% compared to 24% in patients receiving a median amount of 8,8 g/m 2 MTX 28 .…”

“…In fact, another report suggests that higher dose intensity of MTX is a major contributor to favorable outcomes 28 . Patients receiving a median amount of 10,6 g/m 2 MTX showed two‐year overall survival of 50% compared to 24% in patients receiving a median amount of 8,8 g/m 2 MTX 28 . However, poor performance status and high‐risk profile might contribute to reduced MTX dosing and poor outcomes.…”

Primary Central Nervous System Lymphoma Increasing Incidence and Poor Survival: A Finnish Population-based Analysis

“…Worldwide, the prognosis for PCNSL has been dismal. Nevertheless, in recent years, several studies have reported considerable progress in treatment outcomes [9][10][11][12][13]29]. For example, in the International Extranodal Lymphoma Study Group-32 (IELSG-32), the 30-month progression-free survival rate in the group treated with MATRix regimen (methotrexate, cytarabine, thiotepa, and rituximab) was 49%, compared with 23% of those treated with methotrexate-cytarabine alone and 30% of those treated with methotrexate-cytarabine plus rituximab [11].…”

“…The prognosis for PCNSL has been poor, but several clinical trials with relatively short follow-up times have reported considerable progress in treatment outcomes among selected clinical trial populations [9][10][11][12][13]. However, this is in contrast to most of the population-based reports, which have demonstrated only minor improvement in long-term survival [1][2][3][4][5][6].…”

Diagnostic Biomarkers in Cerebrospinal Fluid in Primary Central Nervous System Lymphoma: A Protocol for Systematic Review and Meta-Analysis

“…It responds poorly to conventional chemotherapy, and the overall 5-year survival rate is only about 33% [5]. Combination chemotherapy with high-dose methotrexate, whole brain radiotherapy, and autologous hematopoietic stem cell transplantation can bene t PCNSL patients [6][7][8][9]. In recent years, novel targeted therapeutics have been emerging as potential treatments for PCNSL [10].…”