Drug updated on 11/1/2024
| Dosage Form | Tablet (oral; 20 mg, 50 mg, 70 mg, 80 mg, 100 mg, and 140 mg) |
| Drug Class | Kinase inhibitors |
| Ongoing and Completed Studies | ClinicalTrials.gov |
Indication
- Indicated for the treatment of newly diagnosed adults with Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in chronic phase
- Indicated for the treatment of adults with chronic, accelerated, or myeloid or lymphoid blast phase Ph+ CML with resistance or intolerance to prior therapy including imatinib
- Indicated for adults with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) with resistance or intolerance to prior therapy
- Indicated for the treatment of pediatric patients 1 year of age and older with Ph+ CML in chronic phase
- Indicated for the treatment of pediatric patients 1 year of age and older with newly diagnosed Ph+ ALL in combination with chemotherapy.
Latest News
Summary
- This summary is based on the review of 12 systematic review(s)/meta-analysis(es). [1-12]
- Second-generation TKIs (dasatinib, nilotinib, radotinib) demonstrate improved Major Molecular Response (MMR) and Complete Cytogenetic Response (CCyR) over imatinib, with imatinib 800 mg yielding better outcomes than imatinib 400 mg.
- New-generation TKIs (bosutinib, nilotinib, ponatinib) achieve higher MMR rates at 1 year compared to imatinib, with NG-TKIs (dasatinib, nilotinib, bosutinib, radotinib, ponatinib) also showing improvements in early molecular response at 3 months and in MR4.5.
- No significant difference was observed in 1-year Overall Survival (OS) between new-generation TKIs and imatinib, although pooled data indicated improved OS and Event-Free Survival (EFS) with TKIs in pediatric Ph+ALL compared to non-TKI treatments.
- Second- and third-generation TKIs are associated with reduced rates of transformation to accelerated/blastic phases compared to imatinib.
- All TKIs led to serious grade 3-4 hematologic adverse events, with dasatinib showing a higher likelihood of causing anemia, bosutinib thrombocytopenia, and imatinib neutropenia. Nilotinib and flumatinib demonstrated relatively safer profiles concerning severe hematologic adverse events.
- Radotinib (400 mg) and imatinib (800 mg) had the highest associated risk of ALT and AST elevation, indicating increased liver toxicity. Additionally, bosutinib, nilotinib, and ponatinib exhibited higher risks of hepatotoxicity relative to imatinib.
- Second-generation TKIs displayed an increased likelihood of cutaneous adverse events, particularly with nilotinib, followed by radotinib and bosutinib.
- There is no population types or subgroups information available in the reviewed studies.
Product Monograph / Prescribing Information
| Document Title | Year | Source |
|---|---|---|
| Sprycel (dasatinib) Prescribing Information. | 2024 | Bristol-Myers Squibb, Princeton, NJ |
Systematic Reviews / Meta-Analyses
Clinical Practice Guidelines
| Document Title | Year | Source |
|---|---|---|
| Management of chronic myeloid leukemia in children and young adults. | 2022 | Current Hematologic Malignancy Reports |
| A clinician perspective on the treatment of chronic myeloid leukemia in the chronic phase | 2022 | Journal of Hematology & Oncology |
| Acute lymphoblastic leukemia, version 2.2021, NCCN clinical practice guidelines in oncology. | 2021 | Journal of the National Comprehensive Cancer Network |
| Chronic myeloid leukemia, version 2.2021, NCCN clinical practice guidelines in oncology. | 2020 | Journal of the National Comprehensive Cancer Network |
| JSH practical guidelines for hematological malignancies, 2018: I. Leukemia-4. chronic myeloid leukemia. (cml)/myeloproliferative neoplasms (MPN). | 2020 | International Journal of Hematology |
| A British Society for Haematology Guideline on the diagnosis and management of chronic myeloid leukaemia | 2020 | British Journal of Haematology |
| European LeukemiaNet 2020 recommendations for treating chronic myeloid leukemia | 2020 | Leukemia |