Methotrexate re-challenge for recurrent primary central nervous system lymphoma

Area of Science:

• Neuro-oncology
• Clinical pharmacology
• Hematology

Background:

• Primary CNS lymphoma (PCNSL) recurring after methotrexate has a poor prognosis.
• Current salvage therapies for PCNSL often involve different agents to avoid cross-resistance.
• Methotrexate is a highly active agent in PCNSL, making re-challenge a potential strategy for recurrent disease.

Purpose of the Study:

• To evaluate the safety and efficacy of methotrexate re-challenge in patients with recurrent PCNSL.
• To assess response rates, progression-free survival, and overall survival in this patient population.

Main Methods:

• Retrospective review of 39 patients with histologically confirmed PCNSL.
• Patients had previously responded to methotrexate, experienced relapse, and received methotrexate re-challenge.
• Data collected included patient demographics, Karnofsky performance score (KPS), time to relapse, and treatment regimens.

Main Results:

• Objective response rate (ORR) was 85%, with 75% complete response (CR).
• Median progression-free survival (PFS) was 16 months, and median overall survival (OS) was 41 months.
• 1-year OS was 79%, and KPS was a prognostic factor for PFS (p=0.04).

Conclusions:

• Methotrexate re-challenge is a safe and effective salvage strategy for recurrent PCNSL in patients who previously responded to methotrexate.
• The high response rates and survival outcomes suggest retained chemosensitivity.
• Methotrexate re-challenge should be considered for recurrent PCNSL patients with a history of methotrexate response.