LAUSR

CPG2 is an efficient rescue recombinant bacterial enzyme that cleaves MTX into inactive metabolites. As hdMTX is the key agent in PCNSL, delayed MTX excretion (DME), and/or MTX induced nephrotoxicity (MIN) may expose the patients to severe toxicities and prevent the further use of the drug. Little is known on the use of CPG2 and its impact on patient outcome.Objective: To describe the clinical characteristics, indications, risk factors, outcomes of PCNSL patients treated with CPG2. Retrospective analysis of patients from the LOC network database with histologically proven PCNSL, aged >18, who received CPG2 following hdMTX. From 2011 to 2018, 41(3%) of 1236 patients treated with hdMTX used CPG2. Median age: 70 years [46–86], sex ratio M/F 3.6, median KPS 70. Indications of CPG2 were DME (12%), MIN (34%), both (49%). 37/41 (90%) of the patients had either a cardiovascular history (CVH) (76%) or a preexisting chronic kidney disease (CKD) (56%) and 59% had at least one additional risk factor: delayed MTX elimination or renal toxicity in prior cycles (20%), other grade III-IV toxicity (20%), concomitant drugs interfering with MTX excretion (29%), active infection (22%), hypoalbuminemia (59%). Median hdMTX dose was 3 g/m2 [1–3.5], median number of MTX injection received at the time of CPG2: 2[1–6]. At time of the CPG2 administration, median serum creatinine was 185 μmol/l [108–410] and median serum MTX: 25 μmol/l [1–240]. 24% of patients underwent hemodialysis, 76% return to baseline creatinine, in a median of 30 days; no MTX related deaths were reported. Extrarenal grade III-IV toxicities: lymphopenia (46%), neutropenia (22%), mucocutaneous toxicity (15%), thrombopenia (12%), hepatotoxicity (12%), sepsis (12%). Median time to chemotherapy resumption: 26 days (cytarabine-based or hdMTX rechallenge). HdMTX was reintroduced safely in 14 patients (34%) but one. The outcome (ORR, PFS OS) was similar with that expected of patients who would not have had toxicity to MTX. In our study, a small number of patients have received CPG2 regarding the incidence of MIN and DME, probably due to treatment cost. The high frequency of risk factors points out the need of careful attention of this issue and for adapted hdMTX protocol for this vulnerable population. CPG2 treated patients do not have a worse prognosis than expected. A controlled study is warranted to compare the cost/benefit of the management of MIN /DME with or without CPG2.