Abstract Details

Title Pilot Study of Glucarpidase in Combination with Rituximab and Methotrexate (MTX) in CNS Lymphoma (CNSL)

Topic Neuro-oncology

Presentation(s) S14 - Neuro-oncology (1:24 PM-1:36 PM)

Poster/Presentation
Number 003

Objective To explore the empiric use of glucarpidase administered with repeated doses of MTX and rituximab in patients with CNSL

Background

MTX-based regimens are standard treatment for CNSL. Administration requires aggressive hydration and inpatient monitoring to prevent toxicity. Glucarpidase results in rapid and sustained reduction of serum MTX levels without crossing the blood brain barrier. Efficacy of repeated doses is unknown as development of anti-glucarpidase antibodies is described. Empiric use in the treatment of CNSL has not been adequately studied.

Design/Methods

Eligible adult patients had isolated CNSL and KPS ≥ 50. Rituximab with MTX 3 g/m² or 6 g/m² was administered for eight cycles. Glucarpidase was given 24 hours following start of each MTX infusion. MTX concentrations were monitored in serum and CSF.

Results Five of six patients have enrolled to date, with 24 doses of MTX administered (3 g/m² (20) or 6 g/m² (4)), each followed by glucarpidase. Treatment is complete in 2 patients. Glucarpidase resulted in at least a 95% reduction in serum MTX levels within 15 minutes in 23/24 doses (96%). A 93% decrease was seen with the remaining dose. A transient increase in MTX levels above 100 nmol/L followed 8 of 24 doses (33%) (median 290 nmol/L; range 119-516 nmol/L). CSF MTX concentrations following glucarpidase remained cytotoxic in the 2 patients analyzed to date. Radiographic response: complete (1), partial (2), stable (1), not yet evaluable (1). Three grade 3 adverse events (AEs) unrelated to glucarpidase occurred: lung infection (pneumocystis pneumonia), central line infection, and decreased lymphocyte count. There were no grade 4/5 AEs. Anti-glucarpidase antibody data is pending.

Conclusions Administration of glucarpidase 24 hours after MTX results in repeated and consistent rapid reduction of serum MTX levels. In patients analyzed to date, CSF MTX levels remain therapeutic and clinical response is seen. Enrollment is ongoing.

Authors/Disclosures
Lauren Schaff, MD, FAAN (Memorial Sloan Kettering Cancer Center) PRESENTER	Dr. Schaff has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Guidepoint. Dr. Schaff has received personal compensation in the range of $500-$4,999 for serving as a Consultant for ONO. Dr. Schaff has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for BTG Pharmaceuticals. Dr. Schaff has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Servier. An immediate family member of Dr. Schaff has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for MichieHamlett Attorneys at Law. The institution of Dr. Schaff has received research support from BTG, plc. The institution of Dr. Schaff has received research support from Merck. The institution of Dr. Schaff has received research support from DebioPharm.
Ugur Sener, MD (Mayo Clinic)	Dr. Sener has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Servier Pharmaceuticals. Dr. Sener has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Dr. Sener has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion.
Igor T. Gavrilovic, MD (Memorial Sloan Kettering Cancer Center)	Dr. Gavrilovic has nothing to disclose.
Alexandra M. Miller, MD (NYU Langone Department of Neurology)	Dr. Miller has received personal compensation in the range of $500-$4,999 for serving as a Consultant for GSK. Dr. Miller has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Modifi Biosciences.
Jacqueline B. Stone, MD, FAAN (Memorial Sloan-Kettering Cancer Center)	Dr. Stone has nothing to disclose.
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
Mina Lobbous, MD (Cleveland Clinic Foundation)	Dr. Lobbous has nothing to disclose.
	No disclosure on file
	No disclosure on file
	No disclosure on file
Christian Grommes, MD (Memorial Sloan-Kettering Cancer Center)	Dr. Grommes has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ono. Dr. Grommes has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BTG. Dr. Grommes has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. Grommes has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Curis. Dr. Grommes has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Ono.

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