Management of chronic myeloid leukemia in 2023 – common ground and common sense
Abstract With the improving knowledge of CML and its management, the goals of therapy need to be revisited to ensure an optimal use of the BCR::ABL1 TKIs in the frontline and later-line therapy of CML. In the frontline therapy of CML in the chronic phase (CML-CP), imatinib and the three second-gener...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2023-04-01
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| Series: | Blood Cancer Journal |
| Online Access: | https://doi.org/10.1038/s41408-023-00823-9 |
| _version_ | 1797827679565643776 |
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| author | Jayastu Senapati Koji Sasaki Ghayas C. Issa Jeffrey H. Lipton Jerald P. Radich Elias Jabbour Hagop M. Kantarjian |
| author_facet | Jayastu Senapati Koji Sasaki Ghayas C. Issa Jeffrey H. Lipton Jerald P. Radich Elias Jabbour Hagop M. Kantarjian |
| author_sort | Jayastu Senapati |
| collection | DOAJ |
| description | Abstract With the improving knowledge of CML and its management, the goals of therapy need to be revisited to ensure an optimal use of the BCR::ABL1 TKIs in the frontline and later-line therapy of CML. In the frontline therapy of CML in the chronic phase (CML-CP), imatinib and the three second-generation TKIs (bosutinib, dasatinib and nilotinib) are associated with comparable survival results. The second-generation TKIs may produce earlier deep molecular responses, hence reducing the time to reaching a treatment-free remission (TFR). The choice of the second-generation TKI versus imatinib in frontline therapy is based on the treatment aims (survival, TFR), the CML risk, the drug cost, and the toxicity profile with respect to the patient’s comorbidities. The TKI dosing is more flexible than has been described in the registration trials, and dose adjustments can be considered both in the frontline and later-line settings (e.g., dasatinib 50 mg frontline therapy; dose adjusted schedules of bosutinib and ponatinib), as well as during an ongoing TKI therapy to manage toxicities, before considering changing the TKI. In patients who are not candidates for TFR, BCR::ABL1 (International Scale) transcripts levels <1% are acceptable, result in virtually similar survival as with deeper molecular remissions, and need not warrant a change of TKI. For patients with true resistance to second-generation TKIs or with the T315I gatekeeper mutation, the third-generation TKIs are preferred. Ponatinib should be considered first because of the cumulative experience and results in the CML subsets, including in T315I-mutated CML. A response-based dosing of ponatinib is safe and leads to high TKI compliance. Asciminib is a third-generation TKI with possibly a better toxicity profile, but lesser activity in T315I-mutated CML. Olverembatinib is another potent third-generation TKI with early promising results. |
| first_indexed | 2024-04-09T12:52:13Z |
| format | Article |
| id | doaj.art-f3199252ca5c405e9dd66942feadd154 |
| institution | Directory Open Access Journal |
| issn | 2044-5385 |
| language | English |
| last_indexed | 2024-04-09T12:52:13Z |
| publishDate | 2023-04-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Blood Cancer Journal |
| spelling | doaj.art-f3199252ca5c405e9dd66942feadd1542023-05-14T11:08:58ZengNature Publishing GroupBlood Cancer Journal2044-53852023-04-0113111210.1038/s41408-023-00823-9Management of chronic myeloid leukemia in 2023 – common ground and common senseJayastu Senapati0Koji Sasaki1Ghayas C. Issa2Jeffrey H. Lipton3Jerald P. Radich4Elias Jabbour5Hagop M. Kantarjian6Department of Leukemia, The University of Texas MD Anderson Cancer CenterDepartment of Leukemia, The University of Texas MD Anderson Cancer CenterDepartment of Leukemia, The University of Texas MD Anderson Cancer CenterCancer Clinical Research Unit, Princess Margaret Cancer CentreClinical Research Division, Fred Hutchinson Cancer CenterDepartment of Leukemia, The University of Texas MD Anderson Cancer CenterDepartment of Leukemia, The University of Texas MD Anderson Cancer CenterAbstract With the improving knowledge of CML and its management, the goals of therapy need to be revisited to ensure an optimal use of the BCR::ABL1 TKIs in the frontline and later-line therapy of CML. In the frontline therapy of CML in the chronic phase (CML-CP), imatinib and the three second-generation TKIs (bosutinib, dasatinib and nilotinib) are associated with comparable survival results. The second-generation TKIs may produce earlier deep molecular responses, hence reducing the time to reaching a treatment-free remission (TFR). The choice of the second-generation TKI versus imatinib in frontline therapy is based on the treatment aims (survival, TFR), the CML risk, the drug cost, and the toxicity profile with respect to the patient’s comorbidities. The TKI dosing is more flexible than has been described in the registration trials, and dose adjustments can be considered both in the frontline and later-line settings (e.g., dasatinib 50 mg frontline therapy; dose adjusted schedules of bosutinib and ponatinib), as well as during an ongoing TKI therapy to manage toxicities, before considering changing the TKI. In patients who are not candidates for TFR, BCR::ABL1 (International Scale) transcripts levels <1% are acceptable, result in virtually similar survival as with deeper molecular remissions, and need not warrant a change of TKI. For patients with true resistance to second-generation TKIs or with the T315I gatekeeper mutation, the third-generation TKIs are preferred. Ponatinib should be considered first because of the cumulative experience and results in the CML subsets, including in T315I-mutated CML. A response-based dosing of ponatinib is safe and leads to high TKI compliance. Asciminib is a third-generation TKI with possibly a better toxicity profile, but lesser activity in T315I-mutated CML. Olverembatinib is another potent third-generation TKI with early promising results.https://doi.org/10.1038/s41408-023-00823-9 |
| spellingShingle | Jayastu Senapati Koji Sasaki Ghayas C. Issa Jeffrey H. Lipton Jerald P. Radich Elias Jabbour Hagop M. Kantarjian Management of chronic myeloid leukemia in 2023 – common ground and common sense Blood Cancer Journal |
| title | Management of chronic myeloid leukemia in 2023 – common ground and common sense |
| title_full | Management of chronic myeloid leukemia in 2023 – common ground and common sense |
| title_fullStr | Management of chronic myeloid leukemia in 2023 – common ground and common sense |
| title_full_unstemmed | Management of chronic myeloid leukemia in 2023 – common ground and common sense |
| title_short | Management of chronic myeloid leukemia in 2023 – common ground and common sense |
| title_sort | management of chronic myeloid leukemia in 2023 common ground and common sense |
| url | https://doi.org/10.1038/s41408-023-00823-9 |
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