Primary central nervous system lymphoma
ICD-10 C83.8 ICD-11 2A81.5

Treatment of Primary CNS Lymphoma in Patients Unfit for HD-MTX Due to Advanced Age, Frailty, or Comorbidities

A subset of patients diagnosed with primary central nervous system lymphoma cannot receive high-dose methotrexate (HD-MTX)-based chemotherapy — the standard-of-care backbone — because of advanced age, frailty, or significant comorbidities. This distinct clinical situation requires a different therapeutic approach centred on palliative intent.

Clinical scenario
Less than 15% of patients with primary CNS lymphoma are considered unfit for HD-MTX-containing therapy based on advanced age, frailty, or comorbidities. These patients require careful selection of treatment options that balance disease control with tolerability.
Treatment approach (partial overview)
Palliative treatment options exist for this population, including the use of corticosteroids and certain oral agents, with or without additional systemic therapy. Whole-brain radiotherapy delivered at a palliative dose is also among the approaches considered. Off-label options in this setting are under ongoing evaluation. Full regimen details, sequencing, and dosing guidance are available in the complete structured protocol.
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References

DOI: 10.1016/j.annonc.2023.11.010

Less than 15% of patients with PCNSL are considered unfit for HD-MTX-containing therapy based on advanced age, frailty or comorbidities.

Suitable treatment options include corticosteroids, oral alkylating agents (temozolomide, carmustine, procarbazine) with or without rituximab and WBRT.

When WBRT is used as palliative treatment, a dose of 30-36 Gy/10 or 15 fractions is suggested.

Novel active drugs such as Bruton tyrosine kinase (BTK) inhibitors and immunomodulators may represent off-label alternatives for these patients.

Valid (but incompletely investigated) palliative options include upfront WBRT, corticosteroids, oral alkylating agents with or without rituximab (not EMA approved, not FDA approved), BTK inhibitors and immunomodulators.

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