Safety

BESPONSA has a BOXED WARNING for VOD and post-HSCT NRM1

  • Hepatotoxicity, including fatal and life-threatening VOD, occurred in patients who received BESPONSA
  • A higher post-HSCT NRM rate occurred in patients receiving BESPONSA
  • Additional warnings and precautions include myelosuppression, infusion-related reactions, QT interval prolongation, and embryo-fetal toxicity. Click here to view Important Safety Information

The most common (≥2%) serious adverse reactions (ARs) were infection (23%), febrile neutropenia (11%), hemorrhage (5%), abdominal pain (3%), pyrexia (3%), VOD (2%), and fatigue (2%)1,2

  • The most common (≥2%) ARs reported as the reason for permanent discontinuation were infection, thrombocytopenia, hyperbilirubinemia, transaminases increased, and hemorrhage
  • The most common (≥5%) ARs reported as the reason for dosing interruption were neutropenia, infection, thrombocytopenia, transaminases increased, and febrile neutropenia
  • The most common (≥1%) ARs reported as the reason for dose reduction were neutropenia, thrombocytopenia, and transaminases increased

Common (≥10%) ARs1,a-c

  • Safety was reported in a total of 307 patients, including 164 patients receiving BESPONSA and 143 patients receiving SC

 

 

ALP=alkaline phosphatase; GGT=gamma-glutamyltransferase; HSCT=hematopoietic stem cell transplant; NRM=non-relapse mortality; SC=standard chemotherapy; VOD=hepatic veno-occlusive disease.

aOnly ARs with ≥10% incidence in the BESPONSA arm are included.

bARs included treatment-emergent all-causality events that commenced on or after Cycle 1 Day 1, within 42 days after the last dose of BESPONSA, but prior to the start of a new anticancer treatment (including HSCT).

cARs were graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 3.0.

d19 patients randomized to the SC arm did not receive treatment.

 

References
  1. BESPONSA Prescribing Information. New York, NY: Pfizer Inc.
  2. Data on file. Pfizer Inc, New York, NY.

 

Laboratory abnormalities1

  • Common (≥10%) Grade 3/4 laboratory abnormalities with BESPONSA were neutrophil count decreased, leukocytes decreased, platelet count decreased, lymphocytes (absolute) decreased, hemoglobin decreased, GGT increased, and lipase increased

 

 

ALP=alkaline phosphatase; ALT=alanine aminotransferase; AST=aspartate aminotransferase; GGT=gamma-glutamyltransferase; SC=standard chemotherapy.

 

Reference
  1. BESPONSA Prescribing Information. New York, NY: Pfizer Inc.

 

Incidence and management of VOD

In the INO-VATE ALL study, 23 out of 164 patients (14%) treated with BESPONSA experienced VOD1

Without HSCT

  • During treatment with BESPONSA or in follow-up without an HSCT, 5 out of 164 patients (3%) experienced VOD

With HSCT

  • Among patients who proceeded to HSCT, 18 out of 79 patients (23%) experienced VOD
    • In total, 5 fatal VOD events occurred post HSCT

Median time to onset of VOD post HSCT1

HSCT conditioning regimens containing 2 alkylating agents and last total bilirubin ≥ ULN before HSCT were significantly associated with an increased risk of VOD.1

CR=complete remission; CRi=complete remission with incomplete hematology recovery; HSCT=hematopoietic stem cell transplant; MRD=minimal residual disease; ULN=upper limit of normal; VOD=hepatic veno-occlusive disease.

VOD risk factors to consider for all patients1

  • Increased age
  • Later salvage lines
  • Ongoing or prior liver disease
  • Prior HSCT

Monitoring and management for all patients1

  • A greater number of treatment cycles with BESPONSA was associated with an increased risk of VOD
  • Monitor closely for signs and symptoms of VOD; these may include elevations in total bilirubin, hepatomegaly (which may be painful), rapid weight gain, and ascites
  • Monitor liver tests, including ALT, AST, total bilirubin, and alkaline phosphatase, prior to and following each dose of BESPONSA
    • Elevation of liver tests may require dosing interruption, dose reduction, or permanent discontinuation of BESPONSA
  • Permanently discontinue BESPONSA if VOD (any grade) occurs

Post-HSCT NRM

VOD and infections were the most common causes of post-HSCT NRM1

  • Overall, 48% of patients with BESPONSA received HSCT vs 22% with SC
  • Post-HSCT NRM was higher with BESPONSA (39%; 31/79) vs SC (23%; 8/35), resulting in higher Day 100 mortality

ALT=alanine aminotransferase; AST=aspartate aminotransferase; NRM=non-relapse mortality; SC=standard chemotherapy.

 

Reference
  1. BESPONSA Prescribing Information. New York, NY: Pfizer Inc.