Half-dose glucarpidase: an effective rescue for toxic methotrexate plasma concentrations in a patient with bilateral primary vitreoretinal lymphoma

Primary vitreoretinal lymphoma (PVRL) is a rare, aggressive subtype of central nervous system lymphoma that initially presents in the eye. High-dose methotrexate (HD-MTX) is a key component of systemic therapy, but its use can be complicated by nephrotoxicity and delayed drug clearance, requiring urgent management to avoid toxicity. We report the case of a 29-year-old man with bilateral PVRL receiving treatment with the MATRIX regimen. During the fourth cycle, the patient developed acute kidney injury following intravenous HD-MTX (3.5 g/m²), despite prophylactic measures including hydration, urinary alkalinization, and folinic acid rescue. Plasma MTX concentrations remained elevated at 32 µmol/L at 23 hours and 20 µmol/L at 42 hours post-infusion. A reduced glucarpidase dose (25 U/kg), half the standard dose, was administered 50 hours post-infusion, lowering MTX plasma concentrations by 94.6% from the pre-glucarpidase MTX concentration. Intensified folinic acid rescue was maintained. This case demonstrates that MTX clearance may be impaired, highlighting the importance of early therapeutic drug monitoring. Although the standard glucarpidase dose is 50 U/kg, emerging evidence supports the effectiveness of lower doses, which may offer similar clinical benefit while reducing costs. This consideration is particularly relevant in adults, as weight-based dosing substantially increases drug requirements and treatment costs compared to paediatric patients. Low-dose glucarpidase (25 U/kg) proved effective and safe in treating HD-MTX-induced nephrotoxicity in this patient, offering a cost-effective alternative in settings with limited availability of rescue agents, emphasizing the need for timely intervention and multidisciplinary coordination.