Contributions
Abstract: PB1588
Type: Publication Only
Session title: Infections in hematology (incl. supportive care/therapy)
Background
High-dose methotrexate (MTX) is a key agent for several chemotherapy regimens for various disease states. Its main role relates to its ability to penetrate the central nervous system. Toxicity due to inefficient MTX clearance (Cl) can lead to significant morbidity and mortality. Glucarpidase (GP) is a recombinant enzyme that rapidly reduces MTX concentrations and is currently approved by the United States Food and Drug Administration for patients with toxic MTX concentrations associated with delayed Cl due to impaired renal function. Literature regarding its utilization in the off-trial setting is sparse and mainly limited to case reports. Available literature does not frequently address other issues which could concurrently impact MTX Cl and toxicity, such as supportive care measures or alternative causes of delayed drug elimination.
Aims
To assess the real-world utilization, safety, and efficacy of GP in malignant hematology patients receiving high-dose MTX at a single tertiary care cancer institution who developed MTX-related toxicity and delayed Cl.
Methods
A retrospective, single-center chart review of 19 adults with hematological malignancies who received GP after high-dose MTX-based therapy at Moffitt Cancer Center from January 1, 2012 to November 24, 2020 was conducted. Data collected was descriptive in nature and focused on patient demographics, GP utilization, supportive care measures, and outcomes.
Results
Patient demographics, GP utilization, and supportive care measures are featured in Table 1. Subjects received a median 5000 units (range 2000-7000 units) of GP at a median of 54 hours (range 40-86 hours) post-MTX initiation. Fifteen patients had drug levels available ~36-48 hours after MTX initiation (the remaining four’s last MTX levels were well before this timeframe and would have skewed the comparison). GP resulted in a median 93% (range 15-97%) decrease in those concentrations at a median of 73 hours (range 61-84 hours) after enzyme administration. No significant adverse events related to GP occurred. The most common MTX-related toxicities included nephrotoxicity (N=19, 100%), neutropenia (N=6, 32%), hepatotoxicity (N=4, 21%), and infection (N=4, 21%). Serum creatinine (SCr) increased a median of 200% (range 38-700%) and renal recovery, defined as SCr return to within 50% above baseline SCr, occurred in fifteen patients (79%) at a median of 14 days (range 4-48 days). Median total duration of hospital stay (from initial admission to discharge) was 15 days (range 9-45 days), while median time to MTX Cl (level ≤ 0.1 μm/L) in the sixteen patients achieving that concentration was 12 days (range 5-19 days). One patient (5%) was rechallenged with MTX in the future and did not require GP. Three (16%) and four patients (21%) experienced 30- and 100-day mortality, respectively. Three subjects (15%) died of toxicity directly attributed to MTX.
Conclusion
In this single institution study of malignant hematology patients GP was safe and efficacious in reducing MTX concentrations in patients with delayed Cl, potentially decreasing MTX-related morbidity and mortality. This analysis provides an important insight on the use and activity of GP in the real-world setting for this feared situation. Further studies with larger numbers of patients will be needed in order to analyze factors that can accurately identify patients who will likely need GP.
Keyword(s): Methotrexate
Abstract: PB1588
Type: Publication Only
Session title: Infections in hematology (incl. supportive care/therapy)
Background
High-dose methotrexate (MTX) is a key agent for several chemotherapy regimens for various disease states. Its main role relates to its ability to penetrate the central nervous system. Toxicity due to inefficient MTX clearance (Cl) can lead to significant morbidity and mortality. Glucarpidase (GP) is a recombinant enzyme that rapidly reduces MTX concentrations and is currently approved by the United States Food and Drug Administration for patients with toxic MTX concentrations associated with delayed Cl due to impaired renal function. Literature regarding its utilization in the off-trial setting is sparse and mainly limited to case reports. Available literature does not frequently address other issues which could concurrently impact MTX Cl and toxicity, such as supportive care measures or alternative causes of delayed drug elimination.
Aims
To assess the real-world utilization, safety, and efficacy of GP in malignant hematology patients receiving high-dose MTX at a single tertiary care cancer institution who developed MTX-related toxicity and delayed Cl.
Methods
A retrospective, single-center chart review of 19 adults with hematological malignancies who received GP after high-dose MTX-based therapy at Moffitt Cancer Center from January 1, 2012 to November 24, 2020 was conducted. Data collected was descriptive in nature and focused on patient demographics, GP utilization, supportive care measures, and outcomes.
Results
Patient demographics, GP utilization, and supportive care measures are featured in Table 1. Subjects received a median 5000 units (range 2000-7000 units) of GP at a median of 54 hours (range 40-86 hours) post-MTX initiation. Fifteen patients had drug levels available ~36-48 hours after MTX initiation (the remaining four’s last MTX levels were well before this timeframe and would have skewed the comparison). GP resulted in a median 93% (range 15-97%) decrease in those concentrations at a median of 73 hours (range 61-84 hours) after enzyme administration. No significant adverse events related to GP occurred. The most common MTX-related toxicities included nephrotoxicity (N=19, 100%), neutropenia (N=6, 32%), hepatotoxicity (N=4, 21%), and infection (N=4, 21%). Serum creatinine (SCr) increased a median of 200% (range 38-700%) and renal recovery, defined as SCr return to within 50% above baseline SCr, occurred in fifteen patients (79%) at a median of 14 days (range 4-48 days). Median total duration of hospital stay (from initial admission to discharge) was 15 days (range 9-45 days), while median time to MTX Cl (level ≤ 0.1 μm/L) in the sixteen patients achieving that concentration was 12 days (range 5-19 days). One patient (5%) was rechallenged with MTX in the future and did not require GP. Three (16%) and four patients (21%) experienced 30- and 100-day mortality, respectively. Three subjects (15%) died of toxicity directly attributed to MTX.
Conclusion
In this single institution study of malignant hematology patients GP was safe and efficacious in reducing MTX concentrations in patients with delayed Cl, potentially decreasing MTX-related morbidity and mortality. This analysis provides an important insight on the use and activity of GP in the real-world setting for this feared situation. Further studies with larger numbers of patients will be needed in order to analyze factors that can accurately identify patients who will likely need GP.
Keyword(s): Methotrexate