High-dose methotrexate (MTX) is the main componement of first line treatment in primary central nervous system lymphoma. Renal toxicity is the main dose limiting toxicity because of major MTX elimination by the kidneys. MTX crystallizes in renal tubules, leading to a renal failure (RF) and further delaying its elimination. When RF occurs, MTX accumulates, prolonging the duration of treatment exposure. MTX prolonging exposure can cause life-threatening complications and delay further treatments in the patient. Preventive measures have been developped, such as alkaline fluid hyperhydration and folic acid administration, to try to reduce the risk of these adverse events.

In suspected severe RF in link to MTX is suspected, glucarpidase can be administared. However, this is an expensive treatment and not all patients recover normal renal function despite its use.

MTX is an essential treatment for the management of PCNSL which is currently a curable disease especially in patients who are able to receive a consolidation treatment as thiotepa-based intensive consolidation followed by autologous stem cell transplantation (IC-ASCT). IC-ASCT requires a normal renal function, which could be impaired by severe RF secondary to MTX.

The purpose of the study is to investigate how early dosing MTX could be used to simulate late concentrations. Early monitoring of MTX elimination could be implemented to identify patients at risk of delayed elimination and thus introduce rapid mesures as early administration of glucarpidase.

Inclusion Criteria:

• Adult patient aged 18 years or older,
• Patient with a primary lymphoma of the central nervous system, histologically or cytologically proven,
• Patient eligible for high-dose methotrexate treatment (> at 500 mg/m 2), in the first line of treatment,
• Patient who has received information regarding the study and signed an informed consent,
• Patient beneficiary or entitled to a social security scheme.

Exclusion Criteria:

• Patient treated with a therapy complementary to the standard 1st-line treatment based on high-dose MTX as part of a clinical research protocol,
• Patient in a period of exclusion from another research protocol at the time of signing consent,
• Subjects covered by articles L1121-5 to 1121-8 of the Public Health Code (minor patient, adult patient under guardianship or curatorship, patient deprived of liberty, pregnant or breastfeeding woman).