Results of a large population-based study of patients with primary CNS lymphoma diagnosed between 2011 and 2016 showed a higher proportion of patients 60 years and older compared with reports from studies conducted 1 to 2 decades earlier. The findings from this study were published in Neurology.
Primary CNS lymphoma is a rare, aggressive form of non-Hodgkin lymphoma that can involve the brain, spine, leptomeninges, and eyes. It is characterized by the absence of systemic disease, and a poor prognosis.
A number of advances in the treatment of patients with this disease have been made over the past 3 decades. These have included replacement of conventional whole-brain radiotherapy (WBRT) alone with combined modality therapy including high-dose methotrexate-based chemotherapy followed by WBRT consolidation, which was shown to prolong time to recurrence in these patients. Alternatively, the use of first-line, high-dose chemotherapy followed by autologous stem cell transplantation (ASCT) consolidation is an approach designed to circumvent WBRT-associated toxicity.
In addition, studies of the safety and efficacy of combining first-line high-dose methotrexate with other drugs, such as high-dose cytarabine or rituximab, have shown promising results, although concerns related to toxicity, particularly in older patients, remain with some of these approaches.
This retrospective study included patient-, disease-, and treatment-related data for all adult, HIV-negative patients with primary CNS lymphoma diagnosed between 2011 and 2016 who were included in the French oculo-cerebral lymphoma network, a prospective, nationwide database.
Of the 1002 patients included in this analysis, the median patient age was 68 years (range, 18-91 years), and the median Karnofsky Performance Status (KPS) was 60. Patients at least 60 years old and at least 70 years old comprised 72% and 43% of the study population, respectively.
These data “are in line with epidemiologic studies reporting a continuously increasing rate in the elderly over the last decades,” the study authors commented.
More than 90% of patients were treated with high-dose methotrexate chemotherapy, including more than 80% of patients aged 80 years or older, although the dose was more likely to be lower in the latter population.
Consolidation therapy with WBRT or ASCT was received by 15% and 6% of patients, respectively, although the majority of these patients were younger than 60, with only 11% of patients aged 60 years or older receiving consolidation therapy.
The objective response rate (ORR) to first-line treatment was significantly higher in younger patients compared with older patients (73% vs 54%; P <.001), and ORRs for the overall population and the population treated with consolidation therapy were 59% and 92%, respectively.
At a median follow-up of 44.4 months, the median overall survival (OS) for the overall population was 25.3 months. Although the rates of 1-, 2-, and 5-year OS for the overall population were 62%, 51%, and 38%, the 5-year OS rate for those treated with first-line high-dose chemotherapy followed by ASCT was 76%.
One-quarter of patients included in the study died within 6 months of primary CNS lymphoma diagnosis, and these patients were more likely to be older (P <.001) and to have a worse KPS at diagnosis (P <.001). Cause of death in this group was determined to be multifactorial in 44% of cases, and included impaired neurologic status due to lymphoma, complications (eg, infections), and/or treatment-related side effects.
Median OS in patients 60 years or older at diagnosis of primary CNS lymphoma was 15.4 months compared with 28.4 months in those younger than 60 years (P <.001).
On multivariate analysis, prognostic factors associated with longer OS included age younger than 60 years (P <.001), KPS of 70 or higher at diagnosis (P <.001), female sex (P =.03), and response to first-line induction chemotherapy (P <.001).
The finding that “age represents not only the strongest prognostic factor of the disease, but also a major risk factor for severe treatment-related neurotoxicity,” prompted the study authors to conclude that these results “should stimulate specific studies devoted to the elderly [with primary CNS lymphoma] to optimize the therapeutic management of this growing vulnerable population.”
Houillier C, Soussain C, Ghesquières H, et al. Management and outcome of primary CNS lymphoma in the modern era: an LOC network study [published online January 6, 2020]. Neurology. doi: 10.1212/WNL.0000000000008900