Safety

BESPONSA has a BOXED WARNING for VOD and post-HSCT NRM2

  • 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

The most common (≥2%) serious adverse reactions (ARs) were infection, febrile neutropenia, hemorrhage, abdominal pain, pyrexia, VOD, and fatigue2

  • The most common (≥2%) ARs reported as the reason for permanent discontinuation of treatment 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

HSCT=hematopoietic stem cell transplantation; NRM=nonrelapse mortality; VOD=veno-occlusive disease.

References
  1. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Acute Lymphoblastic Leukemia V.1.2020. © National Comprehensive Cancer Network, Inc. 2020. All rights reserved. Accessed February 26, 2020. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content or its use or application and disclaims any responsibility for its use or application in any way.
  2. BESPONSA Prescribing Information. New York, NY: Pfizer Inc.

Common (≥10%) adverse reactions (ARs)2*†‡

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

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

ARs 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).

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

§19 patients randomized to the SC arm did not receive treatment.

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

References
  1. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Acute Lymphoblastic Leukemia V.1.2020. © National Comprehensive Cancer Network, Inc. 2020. All rights reserved. Accessed February 26, 2020. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content or its use or application and disclaims any responsibility for its use or application in any way.
  2. BESPONSA Prescribing Information. New York, NY: Pfizer Inc.

Laboratory abnormalities2

  • 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.

References
  1. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Acute Lymphoblastic Leukemia V.1.2020. © National Comprehensive Cancer Network, Inc. 2020. All rights reserved. Accessed February 26, 2020. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content or its use or application and disclaims any responsibility for its use or application in any way.
  2. BESPONSA Prescribing Information. New York, NY: Pfizer Inc.

BESPONSA has a BOXED WARNING for VOD and post-HSCT NRM2

  • Hepatotoxicity, including fatal and life-threatening VOD, occurred in patients who received BESPONSA
  • A higher post-HSCT NRM rate occurred in patients receiving BESPONSA

Evaluate VOD risk factors when considering treatment with BESPONSA

Risk factors significantly associated with VOD2

  • Dual-alkylator conditioning regimens
  • Last total bilirubin prior to HSCT ≥ULN

Other risk factors associated with VOD2

  • Prior HSCT
  • Increased age
  • Prior or ongoing liver disease
  • Later salvage lines
  • Greater number of cycles

Multivariate analysis of VOD risk factors in the INO-VATE ALL study3

*A multivariate analysis from the January 4, 2017, cutoff.

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

Monitoring and management for all patients2

  • 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 ALP, prior to and following each dose of BESPONSA
  • Permanently discontinue treatment if VOD (any grade) occurs

Incidence of VOD in the INO-VATE ALL study

In the INO-VATE ALL study, 23 out of 164 patients (14%) treated with BESPONSA experienced VOD2

  • 18 patients experienced VOD after proceeding to HSCT (of 79 patients who received HSCT)
    • Median time to onset of VOD post HSCT was 15 days (range, 3-57)
    • In total, 5 cases of VOD were fatal
  • 5 patients experienced VOD during treatment or in follow-up without HSCT

Regional VOD incidence by location of trial site in the INO-VATE ALL study3

  • Data suggest that the use of conditioning regimens containing 2 alkylating agents was more common outside the United States4

Post-HSCT NRM

VOD and infections were the most common causes of post-HSCT NRM2

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

ALT=alanine aminotransferase; AST=aspartate aminotransferase; CI=confidence interval; CR=complete remission; CRi=complete remission with incomplete hematology recovery; HR=hazard ratio; HSCT=hematopoietic stem cell transplant; MRD=minimal residual disease; NRM=non-relapse mortality; SC=standard chemotherapy; ULN=upper limit of normal; VOD=veno-occlusive disease.

References
  1. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Acute Lymphoblastic Leukemia V.1.2020. © National Comprehensive Cancer Network, Inc. 2020. All rights reserved. Accessed February 26, 2020. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content or its use or application and disclaims any responsibility for its use or application in any way.
  2. BESPONSA Prescribing Information. New York, NY: Pfizer Inc.
  3. Data on file. Pfizer Inc., New York, NY.
  4. Kantarjian HM, DeAngelo DJ, Advani AS, et al. Hepatic adverse event profile of inotuzumab ozogamicin in adult patients with relapsed or refractory acute lymphoblastic leukaemia: results from the open-label, randomised, phase 3 INO-VATE study. Lancet Haematol. 2017;4(8):e387-e398.