BCR-ABL TKIs Flashcards

Question

What is the class and MOA of Ponatinib?

Answer 1

This drug in the following class: - BCR-ABL TKIs This drug's MOA is as follows: - Inhibits BCR-ABL tyrosine kinase - the abnormal gene product of the Philadelphia chromosome in chronic myeloid leukemia

Answer 2

This drug in the following class: - BCR-ABL TKIs This drug's MOA is as follows: - Inhibits BCR-ABL tyrosine kinase - the abnormal gene product of the Philadelphia chromosome in chronic myeloid leukemia - This drug is a novel first in class STAMP (Specifically Targeting the ASL Myristoyl Pocket) inhibitor. This drug potently inhibits ABL1 kinase activity of the BCR-ABL1 fusion protein via allosteric binding to the ASL myristoyl pocket.

Answer 3

The notable/common monitoring parameters for this drug class are: - CBC weekly for first month, biweekly for the second month, then periodically thereafter - Liver function tests (at baseline and monthly) - In patients who discontinue therapy after a sustained molecular response, monitor BCR-ABL transcript levels and CBC with differential monthly for 1 year, then every 6 weeks for the second year, and every 12 weeks thereafter

Answer 4

The emetic potential of this drug is: - Minimal-Low if <400 mg/day - Moderate-High if >400 mg/day

Answer 5

The emetic potential of this drug is: - Minimal-Low

Answer 6

The emetic potential of this drug is: - Minimal-Low if <400 mg/day - Moderate-High if >400 mg/day

Answer 7

The emetic potential of this drug is: - Minimal-Low

Answer 8

The emetic potential of this drug is: - Minimal-Low

Answer 9

The emetic potential of this drug is: - Minimal-Low

Answer 10

The emetic potential of this drug class is: - Most are Minimal-Low - Bosutinib and Imatinib are Moderate-High if >400 mg/day

Answer 11

Drugs in the class with a moderate-high emetic potential are: - Bosutinib and Imatinib if >400 mg/day

Answer 12

Drugs in the class with a low emetic potential are: - All of them except if >400 mg/day for Bosutinib and Imatinib (Moderate-High)

Answer 13

The administration of this drug is described as follows: - Once Daily

Answer 14

The administration of this drug is described as follows: - Once Daily

Answer 15

The administration of this drug is described as follows: - Usually Once Daily - select regimens are Twice Daily

Answer 16

The administration of this drug is described as follows: - Twice Daily (may influence adherence)

Answer 17

The administration of this drug is described as follows: - Once Daily

Answer 18

The administration of this drug is described as follows: - Usually Once Daily - select regimens are Twice Daily

Answer 19

The general techniques for administration of this drug class is described as follows: - All are once daily except for Nilotinib and select regimens of Imatinib and Asciminib (twice daily)

Answer 20

The notable/common ADRs of this drug class are: - Edema - Thrombocytopenia - Neutropenia - Bleeding

Answer 21

The clinical pearls of this drug class are as follows: - Food and/or medications may enhance or decrease absorption - Neither dasatinib, nilotinib or bosutinib have shown improved overall survival or progression free survival rates compared to imatinib, so choice of first-line therapy should be individualized. - The following should be considered when choosing an agent: - toxicity profile - patient's age and ability to tolerate therapy - adherence/ease of administration - comorbid conditions - drug interactions - cost - feasibility of treatment discontinuation - In patients with disease progression, the selection of an alternative agent in this class is based on prior therapy, concurrent disease states, and/or mutational testing.

Answer 22

Considerations for discontinuation of agents in this class are as follows: - The management of CML as a chronic disease requires long-term therapy which can cause both adverse effects and a financial burden. - Discontinuation of TKI may be feasible in selected patients and with careful monitoring. - Discontinuation of TKI therapy may be considered only in patients who met all of the following criteria: - Chronic phase -CML with no history of accelerated phase or blast crisis - Have been on TKI therapy for at least 3 years with no history of resistance - Had stable molecular response for >2 years on at least 4 tests performed at least 3 months apart - Patients who do quality for TKI discontinuation must have monthly molecular monitoring for the first year following discontinuation, then every 6 weeks during the second year, and quarterly thereafter if still in a major molecular response. - If a patient loses their molecular response, they must have prompt resumption of therapy within 4 weeks.

Answer 23

Considerations for resistence to agents in this class are as follows: - Point mutations in the ABL kinase domain are the most frequent mechanism of secondary resistance to these drugs. - Among mutations in the ABL domain, the presence of the T315i mutation is the most common and displays resistance to all currently available agents except ponatinib and asciminib. - T315i mutation is also associated with disease progression and poorer survival. - Asciminib binds allosterically to the ABL pocket and is less susceptible to mutations that drive resistance. It has demonstrated activity against wild-type BCR-ABL1 and several mutant forms (including T315i), even showing activity in heavily pretreated patients. - Consider performing BCR-ABL kinase domain mutational analysis in patients who fail to achieve the response milestones, patients with any loss of response, or patients who experience disease progression to accelerated phase-CML or blast crisis-CML.

Answer 24

Considerations for interactions with agents in this class are as follows: - Dasatinib, Bosutinib, and Ponatinib require an acidic environment for absorption. - Avoid the use of proton pump inhibitors and separate H2-antagonists by at least two hours.

Answer 25

Considerations for CNS penetration of agents in this class are as follows: - Of the available agents, dasatinib crosses blood-brain barrier to the greatest extent.

BCR-ABL TKIs Flashcards

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