Besponsa

BESPONSA- inotuzumab ozogamicin injection, powder, lyophilized, for solution
Wyeth Pharmaceuticals Inc., a subsidiary of Pfizer Inc.

WARNING: HEPATOTOXICITY, INCLUDING HEPATIC VENO-OCCLUSIVE DISEASE (VOD) (ALSO KNOWN AS SINUSOIDAL OBSTRUCTION SYNDROME and INCREASED RISK OF POST-HEMATOPOIETIC STEM CELL TRANSPLANT (HSCT) NON-RELAPSE MORTALITY

HEPATOTOXICITY, INCLUDING VOD

  • Hepatotoxicity, including fatal and life-threatening VOD occurred in patients with relapsed or refractory acute lymphoblastic leukemia (ALL) who received BESPONSA. The risk of VOD was greater in patients who underwent HSCT after BESPONSA treatment; use of HSCT conditioning regimens containing 2 alkylating agents and last total bilirubin level ≥ upper limit of normal (ULN) before HSCT were significantly associated with an increased risk of VOD.
  • Other risk factors for VOD in patients treated with BESPONSA included ongoing or prior liver disease, prior HSCT, increased age, later salvage lines, and a greater number of BESPONSA treatment cycles.
  • Elevation of liver tests may require dosing interruption, dose reduction, or permanent discontinuation of BESPONSA. Permanently discontinue treatment if VOD occurs. If severe VOD occurs, treat according to standard medical practice [see Dosage and Administration (2.3) and Warnings and Precautions (5.1)].

INCREASED RISK OF POST-HSCT NON-RELAPSE MORTALITY

  • There was higher post-HSCT non-relapse mortality rate in patients receiving BESPONSA, resulting in a higher Day 100 post-HSCT mortality rate [see Warnings and Precautions (5.2)].

1. INDICATIONS AND USAGE

BESPONSA is indicated for the treatment of adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL).

2. DOSAGE AND ADMINISTRATION

2.1 Recommended Dosage

  • Pre-medicate before each dose [see Dosage and Administration (2.2)].
  • For the first cycle, the recommended total dose of BESPONSA for all patients is 1.8 mg/m2 per cycle, administered as 3 divided doses on Day 1 (0.8 mg/m2), Day 8 (0.5 mg/m2), and Day 15 (0.5 mg/m2). Cycle 1 is 3 weeks in duration, but may be extended to 4 weeks if the patient achieves a complete remission (CR) or complete remission with incomplete hematologic recovery (CRi), and/or to allow recovery from toxicity.
  • For subsequent cycles:
    • In patients who achieve a CR or CRi, the recommended total dose of BESPONSA is 1.5 mg/m2 per cycle, administered as 3 divided doses on Day 1 (0.5 mg/m2), Day 8 (0.5 mg/m2), and Day 15 (0.5 mg/m2). Subsequent cycles are 4 weeks in duration. OR
    • In patients who do not achieve a CR or CRi, the recommended total dose of BESPONSA is 1.8 mg/m2 per cycle given as 3 divided doses on Day 1 (0.8 mg/m2), Day 8 (0.5 mg/m2), and Day 15 (0.5 mg/m2). Subsequent cycles are 4 weeks in duration. Patients who do not achieve a CR or CRi within 3 cycles should discontinue treatment.
  • For patients proceeding to hematopoietic stem cell transplant (HSCT), the recommended duration of treatment with BESPONSA is 2 cycles. A third cycle may be considered for those patients who do not achieve CR or CRi and minimal residual disease (MRD) negativity after 2 cycles [see Warnings and Precautions (5.1)].
  • For patients not proceeding to HSCT, additional cycles of treatment, up to a maximum of 6 cycles, may be administered.

Table 1 shows the recommended dosing regimens.

Table 1. Dosing Regimen for Cycle 1 and Subsequent Cycles Depending on Response to Treatment
Day 1 Day 8* Day 15*
Abbreviations: CR=complete remission; CRi=complete remission with incomplete hematologic recovery.
*
+/- 2 days (maintain minimum of 6 days between doses).
Dose is based on the patient’s body surface area (m2).
For patients who achieve a CR or a CRi, and/or to allow for recovery from toxicity, the cycle length may be extended up to 28 days (i.e., 7-day treatment-free interval starting on Day 21).
§
CR is defined as < 5% blasts in the bone marrow and the absence of peripheral blood leukemic blasts, full recovery of peripheral blood counts (platelets ≥ 100 × 109 /L and absolute neutrophil counts [ANC] ≥ 1 × 109 /L) and resolution of any extramedullary disease.
CRi is defined as < 5% blasts in the bone marrow and the absence of peripheral blood leukemic blasts, incomplete recovery of peripheral blood counts (platelets < 100 × 109 /L and/or ANC < 1 × 109 /L) and resolution of any extramedullary disease.
#
7-day treatment-free interval starting on Day 21.
Dosing regimen for Cycle 1
All patients:
Dose 0.8 mg/m2 0.5 mg/m2 0.5 mg/m2
Cycle length 21 days
Dosing regimen for subsequent cycles depending on response to treatment
Patients who have achieved a CR § or CRi :
Dose 0.5 mg/m2 0.5 mg/m2 0.5 mg/m2
Cycle length 28 days #
Patients who have not achieved a CR § or CRi :
Dose 0.8 mg/m2 0.5 mg/m2 0.5 mg/m2
Cycle length 28 days #

2.2 Recommended Pre-medications and Cytoreduction

  • Premedication with a corticosteroid, antipyretic, and antihistamine is recommended prior to dosing. Patients should be observed during and for at least 1 hour after the end of infusion for symptoms of infusion related reactions [see Warnings and Precautions (5.4)].
  • For patients with circulating lymphoblasts, cytoreduction with a combination of hydroxyurea, steroids, and/or vincristine to a peripheral blast count of less than or equal to 10,000/mm3 is recommended prior to the first dose.

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