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Therapie der CML |
Allgemeines |
|
Studien |
Behandlung im Rahmen der Deutschen CML-Studiengruppe empfohlen |
Chemotherapie |
Omacetaxin, Cytarabin, Hydroxyurea, Busulfan |
Targettherapie: TKI |
I.Generation: |
Imatinib 4-800mg/d |
selektiver Inhibitor der BCR-ABL-Thyrosinkinase. |
| II.Generation: |
Dasatinib100mg/d, Nilotinib 600mg/d, Panatinib |
Bei Resistenz gegen Imatinib.
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| III.Generation: |
Ponatinib, Bosutinib |
Zulassung für CLL: chronische Phase, akzelerierte Phase, Blastenkrise |
resistent gegen Dasatinib, ungeeignet für Imatinib oder T315I-Mutation |
Ascinimib, Scemblix® |
Zulassung:
CML
Philsadelphia-Chromosom positiv
Erwachsene
Vorbehandlung: nach >1 TK-Inhibitor |
TKI - Resistenz |
Eine TKI-Resistenz beruht auf Mutation der Kinase . |
Je nach Mutation ist ein anderer TKI zu bevorzugen (1) |
BCR-ABL-Mutation |
F317L/V/I/C - Mutation |
Therapie besser mit TASIGNA® (Nilotinib) oder BOSULIF® (Bosutinib) als mit SPRYEL® (Dasatinib) |
V299L - Mutation |
Therapie besser mit TASIGNA® als mit BOSULIF® oder SPRYCEL® |
Y253F/H, E255K/V, F359V/I/C - Mutation |
Therapie besser mit SPRYCEL® oder BOSULIF® als mit TASIGNA® |
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allogene Stammzelltransplantation |
Milz-Bestrahlung |
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Teil von |
CML |
Leukämie |
Maligne Systemerkrankungen |
Onkologie |
| Quellen |
1.) Jabbour E, Kantarjian H and Cortes J:
Use of Second- and Third-Generation Tyrosine Kinase Inhibitors in the Treatment of Chronic Myeloid Leukemia: An Evolving Treatment Paradigm.
Clinical Lymphoma, Myeloma & Leukemia 2015;15:323-334
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Patients with F317L/V/I/C mutations are more sensitive to TASIGNA® (Nilotinib) or BOSULIF® (Bosutinib) than to SPRYEL® (Dasatinib)
2) Patients with V299L mutation are more sensitive to TASIGNA® than to BOSULIF® or SPRYCEL®
3) Patients with Y253F/H, E255K/V, and F359V/I/C mutations are more sensitive to SPRYCEL® or BOSULIF® than to TASIGNA®
Tolerability of Second Generation TKIs
1) Patients who experience pleural effusion during SPRYCEL® treatment might better tolerate TASIGNA® or BOSULIF®
2) Patients who experience rash during treatment with TASIGNA® or BOSULIF® could be switched to SPRYCEL®
3) Some toxicities common with other TKIs such as pleural effusion and cardiac toxicity are less common with BOSULIF® and this agent also has activity against many BCR-ABL kinase domain mutations resistant to GLEEVEC®, SPRYCEL® and TASIGNA®, with the exception of T315I mutation.
It should be noted that Second generation TKI as third line therapy has limited value in majority of the patients with CML. ICLUSIG® (Ponatinib) is a Third generation kinase inhibitor approved for the treatment of patients with T315I positive CML or T315I-positive Philadelphia Chromosome positive Acute Lymphoblastic Leukemia (Ph+ ALL) and for whom no other TKI is indicated. Other treatment options include SYNRIBO® (Omacetaxine Mepesuccinate), a first-in-class Cephalotaxine and a semi synthetic purified Homoharringtonine (HHT) compound. Unlike Tyrosine Kinase Inhibitors , SYNRIBO® is a protein synthesis inhibitor and reduces the levels of multiple Oncoproteins including BCR-ABL, BCL-2, MCL-1 and promotes apoptosis of leukemic stem cells. This agent is presently approved for the treatment of Chronic or Accelerated phase Chronic Myeloid Leukemia (CML) with resistance and/or intolerance to two or more Tyrosine Kinase Inhibitors, with cytopenias being the most common toxicity. Allogeneic Hematopoietic Stem Cell transplantation should be considered for eligible patients with T315I mutation not responding to ICLUSIG®, those with mutations resistance to second and third generation TKIs and patients with Accelerated or Blast phase CML, following remission with TKIs.
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