PCNSL in Elderly Patients Unsuitable for HDC-ASCT: What to Do After HD-MTX Induction

Clinical scenario

This protocol addresses elderly patients with primary central nervous system lymphoma who cannot undergo high-dose chemotherapy with autologous stem cell transplantation (HDC-ASCT) — due to advanced age, poor performance status, or significant comorbidities — but who retain adequate renal function (eGFR ≥50 ml/min) and are fit for HD-MTX-based chemotherapy.

Previous treatment & escalation condition

The prior line — HD-MTX-based induction chemotherapy (in combinations such as MPV-A, MT, ReMP, or ReMT) — targets achievement of complete remission or partial response assessed by gadolinium-enhanced brain MRI every two cycles. When those targets are not reached, or when myeloablative consolidation remains contraindicated in this population, this protocol defines the structured management path.

Management approach (partial overview)

For patients with responsive disease after induction, this protocol outlines consolidation and maintenance strategies — including a radiotherapy-based approach and oral maintenance options — alongside defined criteria for active surveillance. Full sequencing and eligibility criteria are in the complete structured regimen.

Instant Access to Structured Evidence-Based Regimens

References

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.

Reduced-dose WBRT (23.4 Gy) is an option for patients with responsive disease after suitable induction ChT, but the longer-term effects on cognitive function remain to be defined, especially in elderly patients.

In the randomised ALLIANCE 51101 study, consolidation with non-myeloablative HD-AraCeetoposide was compared with carmustineethiotepa-conditioned ASCT in 108 patients aged 18-75 years with PCNSL.

Watchful waiting can be considered in elderly patients in CR after induction with an established drug combination. Maintenance with oral drugs, such as alkylating agents or immunomodulators such as lenalidomide (not EMA approved, not FDA approved) can be considered on an individual basis.

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