Real-World Evidence

DATA PUBLISHED JANUARY 2025

Real-world evidence supports the use of VORAXAZE in patients with HDMTX-induced AKI1

Study design details1

Investigators from Mass General Brigham (Boston, MA) analyzed outcomes in 708 adult patients with HDMTX-induced AKI across 28 leading US cancer centers from 2000 to 2022 using a target trial emulation framework. This applied the core principles of randomized controlled trials and was the largest observational study of its kind.

708 patients
Primary outcome1
  • Kidney recovery at the time of hospital discharge (defined as a composite of survival to hospital discharge without kidney replacement therapy dependence and with serum creatinine <1.5-fold baseline)
Secondary outcomes1
  • Time to kidney recovery in the first 14 days
  • Incidence and severity of neutropenia, transaminitis, and mucositis on Day 7 (±2) following MTX initiation

LIMITATIONS: This was an observational, non-randomized study, which limits the ability to draw causal conclusions. The timing of VORAXAZE administration was not standardized, and optimal timing remains uncertain. Methotrexate levels were not consistently available for all patients, which may affect interpretation of efficacy. Findings may not be generalizable to all settings. VORAXAZE-treated patients had longer hospital stays than non-VORAXAZE–treated patients and, therefore, may have had more time to recover.1

This study was funded by BTG International Ltd, a SERB Pharmaceuticals company.

Patients who received VORAXAZE within 4 days of initiation of HDMTX were observed to have improved outcomes compared with those who did not1,*

2.7x
Primary endpoint1

Higher likelihood of renal recovery by hospital discharge

OR, 2.70 (95% CI, 1.69-4.31) Adjusted OR of kidney recovery in patients treated with VORAXAZE

clockEndpoint
Secondary endpoint1

Faster time to renal recovery in the first 14 days following HDMTX-induced AKI

HR, 1.88 (95% CI, 1.18-3.33) Adjusted HR in patients treated with VORAXAZE. By Day 14, 36.1% of patients who received VORAXAZE had renal recovery, compared with 24.4% of patients who did not

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Secondary endpoint1

Lower likelihood of Grade ≥2 neutropenia and Grade ≥2 transaminitis at Day 7

OR, 0.50 (95% CI, 0.28-0.91)
and
OR, 0.31 (95% CI, 0.13-0.77) Adjusted OR in patients treated with VORAXAZE

Median time point of VORAXAZE administration following initiation of MTX1

Median dose received1

LIMITATIONS: This was an observational, non-randomized study, which limits the ability to draw causal conclusions. The timing of VORAXAZE administration was not standardized, and optimal timing remains uncertain. Methotrexate levels were not consistently available for all patients, which may affect interpretation of efficacy. Findings may not be generalizable to all settings. VORAXAZE-treated patients had longer hospital stays than non-VORAXAZE–treated patients and, therefore, may have had more time to recover.1

  • *

    Data from a controlled, observational study assessing clinical outcomes across 708 adults with HDMTX-induced AKI from 28 major US cancer centers from 2000 to 2022. Two hundred nine (29.5%) patients were treated with VORAXAZE within 4 days following MTX exposure, and 499 (70.5%) were not. The primary outcome was kidney recovery at the time of hospital discharge, defined as a composite of survival to hospital discharge without kidney replacement therapy dependence and with serum creatinine <1.5-fold baseline. Secondary outcomes included time to kidney recovery in the first 14 days and incidence and severity of neutropenia, transaminitis, and mucositis on Day 7 (±2) following MTX initiation.1

Health Economics Icon

ESTIMATE POTENTIAL BUDGET IMPACT OF VORAXAZE USING A HEALTH ECONOMICS MODEL

The VORAXAZE Health Economics Model can help institutions evaluate the potential economic impact of earlier use of VORAXAZE (within 60 hours from the start of HDMTX infusion) vs later use (after 60 hours), dialysis, or supportive care alone (based on institutional data) for patients indicated for VORAXAZE.2,3

  • The model estimates the overall value of VORAXAZE by analyzing costs of associated clinical outcomes (eg, hospital LOS and ICU costs)2-4

  • Schedule a demonstration of this model to see how earlier use of VORAXAZE may benefit your institution

Some patients have been rechallenged with HDMTX following VORAXAZE TREATMENT5,6

IN ADULT PATIENTS

In a retrospective, single-center study of 11 adults with lymphoma who received treatment with VORAXAZE, 7 patients were rechallenged with MTX5: 

Patients completed all 
recommended doses of HDMTX

Median percentage dose reduction from the MTX dose

Patients did not develop repeat AKI from subsequent MTX doses

Patients required VORAXAZE in subsequent MTX cycles

2 out of 7 patients experienced AKI when rechallenged with MTX (n=1, Stage 1; n=1, Stage 2), but completed all recommended doses. The one patient who did not complete all recommended doses was due to disease progression.5

From a retrospective, single-center observational review of 11 adult patients with lymphoma who received at least 1 dose of VORAXAZE for toxic MTX levels between January 2020 and October 2022. Seven of these patients were rechallenged with MTX and received a total of 32 additional MTX doses after VORAXAZE. Time to MTX clearance was defined as the time between the initiation of MTX infusion to the time at which MTX levels fell below 0.1 μM or at the time at which the last MTX level during the hospitalization was obtained.5

LIMITATION: These findings should be interpreted with caution given the retrospective study design and the small sample size.

IN PEDIATRIC PATIENTS

In a retrospective, single-center study that evaluated 20 pediatric patients with cancer who received VORAXAZE, 13 patients were rechallenged with HDMTX6:

Patients completed all recommended doses of HDMTX

Median time point of VORAXAZE administration from start of HDMTX

Median time to HDMTX rechallenge after start of previous HDMTX course

Patients required VORAXAZE in subsequent HDMTX cycles

Of the 2 patients who were rechallenged that did not complete all recommended courses of HDMTX, one patient experienced renal dysfunction and delayed MTX elimination, and another experienced neurotoxicity that was unrelated to renal dysfunction.5

From a retrospective, single-center study that evaluated 20 pediatric patients with cancer who received VORAXAZE for HDMTX-induced acute kidney injury between October 1998 and December 2010. Thirteen of these patients were rechallenged with HDMTX and received a total of 39 additional HDMTX doses after VORAXAZE. Time to complete MTX excretion was defined as the time elapsed between the start of the MTX infusion to the time at which the plasma MTX concentration fell below 0.1 μM or to the time at which the last MTX concentration was obtained for a given HDMTX course for patients whose last documented measurement was not <0.1 μM.6

LIMITATION: These findings should be interpreted with caution given the retrospective study design and the small sample size.

CHOOSE VORAXAZE FOR RAPID, NONRENAL ELIMINATION OF TOXIC MTX7

Administration of VORAXAZE, when indicated, should optimally occur within 48-60 hours from the start of the HDMTX infusion because life-threatening toxicities may not be preventable beyond this time point.2

View efficacy

AKI, acute kidney injury; CI, confidence interval; HDMTX, high-dose methotrexate; HR, hazard ratio; ICU, intensive care unit; LOS, length of stay; MTX, methotrexate; OR, odds ratio.