Primary CNS lymphoma in the real world—Opportunities for improved outcomes in different health settings

Primary central nervous system lymphoma (PCNSL) is a rare and aggressive lymphoproliferative disease accounting for 4% of primary CNS neoplasms.¹ Immunosuppression is the only known risk factor for the development of PCNSL with a high incidence among those with advanced HIV infection. The management of PCNSL typically consists of an induction and consolidation phase, utilizing multidrug methotrexate-based regimens with or without radiation. There is a lack of consensus on the optimum consolidation regimen, in part, due to a lack of randomized data to inform treatment decisions. Following a positive response to induction therapy, patients could be offered consolidation therapy using autologous stem cell transplantation (ASCT), whole-brain radiation therapy (WBRT), or further chemotherapy, with treatment decisions made based on patient and disease characteristics.

Patel et al analyzed sociodemographic barriers impacting the treatment and outcomes of 95 patients with PCNSL at a public safety-net hospital (n = 33) compared to those treated at a private tertiary academic institution (n = 62) between 2007 and 2020.² Patients at both institutions were treated by the same multidisciplinary team. In this study, patients at the safety-net hospital were significantly younger, more likely to be from a racial minority (Hispanic or Black), and be a person living with HIV (PLWH). Patients treated at the public safety-net hospital were significantly less likely to receive induction chemotherapy, which the authors postulated was due to increasing age and the higher number of patients with HIV infection. In this study, PLWH were overrepresented in those attending the public safety-net hospital (46% vs 5% attending the private health service) and were more likely to receive WBRT rather than chemotherapy as induction treatment. While the authors discuss potential reasons for pursuing non-chemotherapy treatment modalities, detailed information about plasma HIV load, CD4 cell count, or the presence or absence of concomitant opportunistic infections at treatment commencement were not available unfortunately to enable a fuller understanding of the management rationale. In those that did receive induction therapy, the hospital setting did not significantly affect whether a patient received consolidation therapy. Importantly, there was no significant difference in response rates to chemotherapy-based induction treatment between safety-net and academic center patients. In addition, patients receiving consolidation therapy at the safety-net hospital were significantly less likely to receive ASCT and had higher rates of consolidative WBRT. This disparity in consolidation options was attributed to lack of access and cost of ASCTs. Lastly, although outcomes were not different in the overall study, the different demographics of the two hospital populations may mask eventual differences in outcome and toxicity data, especially neurotoxicity data, were also limited by the retrospective nature of the study. Although this study reports similar rates of neurotoxicity between the two patient cohorts, the retrospective nature of this study limits the significance of these findings and WBRT-induced severe neurotoxicity remains a major concern. However, these findings are similar to those reported in a retrospective study that analyzed patients with histologically confirmed PCNSL reported to the National Cancer Database between 2004 and 2013.³ In this study, patients treated at academic/research cancer programs were more likely to receive chemotherapy compared with community programs with the omission of chemotherapy associated with increasing age, comorbidities, black race, and indicators of poor socioeconomic status.

These data are important as they raise that different PCNSL populations may be routinely receiving different treatment approaches. At least in the PLWH population, this is potentially understandable given the potential increased risk of treatment-related toxicity particularly if there are comorbidities. However, the importance of not treating these patients is becoming much clearer. There is increasing evidence that induction high-dose methotrexate, used in conjunction with effective antiretroviral therapy (ART), can be used in the majority of patients with HIV-related PCNSL, avoiding WBRT and the associated risk of neurocognitive decline.^4,5 As seen in this study, other studies have also demonstrated long-term disease-free survival in HIV-related primary CNS lymphoma with ART and high-dose methotrexate.^4,5 A recent study prospective also confirmed the safety and feasibility of treating these patients with ART, rituximab, and high-dose methotrexate with good outcomes and minimal neurotoxicity.⁶

In summary, Patel et al provide a valuable real-world perspective of challenges and differences in treating the same disease in different health settings and patient populations. Their data challenge us to prospectively look at these differences and optimize treatments accordingly, while acknowledging the difficulties of doing so in a rare tumor. This is especially in PLWH where the incidence of PCNSL is fortunately dropping due to the availability of effective ART.³