In older adults with primary central nervous system lymphoma, unsuitability for high-dose consolidation is common. When HDC-ASCT is not an option, the treatment approach must balance efficacy with tolerability — guided by performance status, comorbidities, and renal function.
Patients with advanced age (elderly) who are unsuitable for HDC-ASCT due to poor performance status or comorbidities, yet who remain fit for HD-MTX-based chemotherapy with preserved renal function (eGFR ≥50 ml/min). Unsuitability for HDC-ASCT in PCNSL is most commonly related to advanced age, poor performance status, treatment-related toxicity, or comorbidities.
Standard induction treatment in this population is based on HD-MTX-containing combination chemotherapy. Several combination regimens have been evaluated in prospective trials specifically in elderly or less fit patients, each pairing HD-MTX with other cytostatic or targeted agents. The choice of combination and the management of dosing in relation to renal function are central to delivering adequate treatment intensity.
Full regimen details, dosing guidance, renal-function adjustments, and the complete evidence-based algorithm are available in the structured protocol.
The primary aim is achievement of complete remission or partial response, assessed by gadolinium-enhanced brain MRI evaluated every two courses during induction.
DOI: 10.1016/j.annonc.2023.11.010
Unsuitability for HDC-ASCT in patients with PCNSL is mostly related to advanced age, poor PS, treatment-related toxicity or comorbidities.
Standard induction treatment for fit, elderly patients is HD-MTX-based ChT; however, choice of treatment regimen and delivery of adequate dose intensity are therapeutic challenges.
Reducing the dose of MTX is not justified in elderly patients with preserved renal function [estimated glomerular filtration rate (eGFR) 50 ml/min] but should be considered in patients with eGFR <50 ml/min.
Response to treatment should follow IPCG criteria: gadolinium-enhanced MRI of the brain should be carried out every two courses during induction ChT and 2 months after consolidation, and compared with baseline MRI, with the addition of ocular and CSF exams if involved at baseline.
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