LuciPona (Ponatinib)

About Ponatinib 

Ponatinib is a medication used for the treatment of chronic myeloid leukemia and Philadelphia chromosome–positive (Ph+) acute lymphoblastic leukemia.  It is a multi-targeted tyrosine-kinase inhibitor. Some forms of chronic myeloid leukemia, those that have the T315I mutation, are resistant to current therapies such as imatinib. Ponatinib has been designed to be effective against these types of tumors.

Chronic Myeloid Leukemia

Chronic phase (CP) chronic myeloid leukemia (CML)

• Indicated for patients with CP-CML with resistance or intolerance to at least 2 prior kinase inhibitors
• 45 mg PO qDay initially
• Reduce to 15 mg PO qDay upon achievement of ≤1% BCR-ABL1IS
• Re-escalate dose to previously tolerated dosage of 30 mg or 45 mg PO qDay in patients with loss of response
• Continue until loss of response at the re-escalated dose or unacceptable toxicity
• Consider discontinuing treatment if response has not occurred by 3 months

Accelerated phase (AP) or blast phase (BP) CML

• Indicated for AP-CML or BP-CML for whom no other kinase inhibitors are indicated, and for T315I-postive CML (CP, AP, BP)
• Optimal dose not identified
• 45 mg PO qDay
• Consider reducing dose for AP-CML in patients who have achieved a major cytogenetic response
• Continue until loss of response or unacceptable toxicity
• Consider discontinuing treatment if response has not occurred by 3 months

Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia (Ph+ ALL)

Newly diagnosed in combination with chemotherapy

• Indication for Ph+ ALL based on minimal residual disease (MRD)-negative complete remission (CR) at end of induction
• 30 mg PO qDay; reduce to 15 mg PO qDay upon achievement of MRD-negative (≤0.01% BCR::ABL1/ABL1) CR at end of induction
• Continue in combination with chemotherapy for up to 20 cycles (each cycle is 28 days) until loss of response or unacceptable toxicity

• Induction (cycles 1-3)

  • Ponatinib 30 mg PO qDay, plus
  • Vincristine 1.4 mg/m² IV on Days 1 and 14 (not to exceed 2 mg/dose), and
  • Dexamethasone: 40 mg (age <60 yr) or 20 mg (age ≥60 yr) PO on Days 1-4 and Days 11-14

• Consolidation (cycles 4-9, alternating methotrexate and cytarabine)

  • Ponatinib 30 mg (or decreased to 15 mg if in MRD-negative CR) PO qDay, plus
  • Methotrexate (cycles 4, 6, and 8): 1000 mg/m² (age <60 yr) or 250 mg/m² (age ≥60 yr) IV on Day 1, OR
  • Cytarabine (cycles 5, 7, and 9): 1000 mg/m² (age <60 yr) or 250 mg/m² (age ≥60 yr) IV q12hr on Days 1, 3, and 5

• Maintenance (cycles 10-20)

  • Ponatinib 30 mg (or decreased to 15 mg if in MRD-negative CR) PO qDay, plus
  • Vincristine 1.4 mg/m² IV on Day 1 (not to exceed 2 mg/dose), and
  • Prednisone: 200 mg (aged <60 yr) or 100 mg (age ≥60 to 69 yr) or 50 mg (age ≥70 yr) PO on Days 1-5

Monotherapy

• Indicated for patients with Ph+ ALL for whom no other kinase inhibitors are indicated or T315I-postive Ph+ ALL
• Optimal dose not identified
• 45 mg PO qDay initially
• Continue until loss of response or unacceptable toxicity
• Consider discontinuing treatment if response has not occurred by 3 months