Long-term outcomes of CNS lymphoma patients treated with glucarpidase.

2091 Background: High-dose methotrexate (HD-MTX) is the backbone of potentially curative therapy for central nervous system lymphoma (CNSL) but requires inpatient admission for hydration and monitoring to minimize toxicity. Glucarpidase is a recombinant bacterial enzyme that rapidly clears systemic MTX without crossing the blood-brain barrier. It is FDA-approved as a rescue agent in the setting of MTX toxicity. Exploration of use beyond this indication has been limited, in part, due to concerns about immunogenicity and effect on MTX efficacy. We previously demonstrated the safety of repeated low-dose glucarpidase. Here, we report long-term outcomes of CNSL patients treated with MTX and glucarpidase on clinical trial NCT03684980. Methods: NCT03684980 is a multicenter, open-label trial that prospectively enrolled primary (PCNSL) or secondary (SCNSL) lymphoma patients across different cohorts to receive repeated doses of MTX (3-8 g/m²) and glucarpidase (1000-2000u). Patients who received ≥ 6 of 8 planned doses were included. Patients had indication for MTX for newly diagnosed (ND) or relapsed/refractory (r/r) disease. There were no restrictions on post-MTX therapy or consolidation. Objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) were assessed. Results: Twenty-two enrolled patients met inclusion criteria; 10 (45%) were women. Median age was 70 years, and median Karnofsky Performance Status was 80. PCNSL accounted for 20/22 (91%) of cases; 5/22 (23%) were treated for r/r disease. Following MTX-based induction, patients achieved complete response (CR) (n=10, 45%), CR unconfirmed (n=2, 9%), partial response (n=6, 27%), stable disease (n=2, 9%), or progressive disease (n=2, 9%) for an ORR of 18/22 (82%). Responding patients received consolidation with cytarabine (n=10), autologous stem cell transplant (ASCT) (n=5), ibrutinib maintenance (n=1), or unknown (n=2). Median follow-up was 55.5 months. Median PFS and OS were not reached overall. PFS and OS were not reached for PCNSL, versus 7.3 and 21.0 months for SCNSL. PFS was not reached for ND patients versus 12.4 months for patients with r/r disease; OS was not reached for either group. Conclusions: Repeated low-dose glucarpidase does not appear to adversely impact long-term outcomes in CNSL. Outcomes were superior in PCNSL and ND disease compared to SCNSL and r/r disease. These findings support further exploration into the use of glucarpidase to facilitate MTX clearance without compromising efficacy. Clinical trial information: NCT03684980 .