Clinical trial outcome

15.4% (10/65) CR/CRi in patients who received multiple prior therapies1
Remission rate results

CI=confidence interval (Clopper-Pearson); CR=complete remission; CRi=complete remission with
incomplete blood count recovery.

Select Important Safety Information

  • MARQIBO is contraindicated in patients with demyelinating conditions, including Charcot-Marie-Tooth syndrome; in patients with hypersensitivity to vincristine sulfate or any of the other components of MARQIBO; and for intrathecal administration
  • Sensory and motor neuropathy are common and cumulative. Monitor patients for peripheral motor and sensory, central and autonomic neuropathy and reduce, interrupt, or discontinue dosing. Patients with preexisting severe neuropathy should be treated with MARQIBO only after careful risk-benefit assessment

Median duration of CR/CRi

HSCT=hematopoietic stem cell transplant.

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  • MARQIBO is expected to interact with drugs known to interact with nonliposomal vincristine sulfate, therefore the concomitant use of strong CYP3A inhibitors or the use of potent P-glycoprotein inhibitors or inducers should be avoided
  • Deaths occurred in 23% of patients in study 1. The nonleukemia-related causes of death were brain infarct (1), intracerebral hemorrhage (2), liver failure (1), multisystem organ failure (2), pneumonia and septic shock (3), respiratory
    failure (4), pulmonary hemorrhage (1), and sudden cardiac death (1)

 

Clinical trial design

MARQIBO was studied in an international, open-label, multicenter, single-arm phase 2 study (study 1) of adult patients with Ph– ALL1
Study design and outcome measures

*Patients received weekly MARQIBO until response achievement, leukemia progression, toxicity, or decision to pursue other therapy, such as HSCT. Patients with ongoing responses could continue MARQIBO at their physician's discretion. Patients received a median of 4 doses (Range, 1–18).2

  • MARQIBO monotherapy was administered intravenously over 1 hour
    every 7 days1
  • Concomitant corticosteroids were not permitted beyond day 51
  • 72% of doses were given in an outpatient setting in the clinical trial2

Patient characteristics1

  • Enrollment required that patients had to have achieved a CR to at least
    1 prior anti-leukemia chemotherapy, defined by a leukemia-free interval
    of ≥90 days
  • Patients were in second or greater relapse or had disease progression following 2 or more anti-leukemia therapies
  • All patients had previously received non-liposomal (standard) vincristine, and
    80% had evidence of peripheral neuropathy at baseline
  • All patients were ineligible for immediate HSCT at enrollment

Select Important Safety Information

  • The safety and effectiveness of MARQIBO in pediatric patients have not been established
  • It is not known whether MARQIBO is excreted in human milk
  • MARQIBO can cause fetal harm. Advise women of potential risk to fetus

 

Achieves higher AUC

Plasma clearance of MARQIBO is slow, contributing to a high plasma concentration1
  • Plasma clearance of MARQIBO is slow, 345 mL/h, at a dose of 2.25 mg/m2. This is in comparison to the rapid clearance of non-liposomal vincristine sulfate at
    189 mL/min/m2 (11,340 mL/h)
  • Slow clearance of MARQIBO contributes to a much higher area under the
    curve (AUC) for MARQIBO relative to non-liposomal vincristine sulfate
  • Reported vincristine levels reflect liposome-encapsulated drug that may not be immediately bioavailable and may not be directly comparable with plasma levels of vincristine after administration of non-liposomal vincristine, which is immediately bioavailable
Plasma pharmacokinetics of MARQIBO*

*The plasma pharmacokinetics of MARQIBO was investigated in 13 adult patients with relapsed ALL who received MARQIBO 2.25 mg/m2 administered as a 1-hour intravenous infusion. Data reflected in chart are the mean values.
Median AUC=13,680 h•ng/mL (Range, 7036–26,074 h•ng/mL).

Select Important Safety Information

  • Fatal liver toxicity and elevated levels of aspartate aminotransferase have occurred. Monitor liver function and modify or interrupt dosing for hepatic toxicity
  • Severe fatigue can occur requiring dose delay, reduction, or discontinuation of MARQIBO
  • Neutropenia, thrombocytopenia, or anemia may occur. Monitor blood counts prior to each dose. Consider dose modification or reduction as well as supportive care measures if Grade 3 or 4 myelosuppression develops