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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. |
| 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 |
ASC4FIRST-Studie(2) |
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
2.) Hochhaus A, et al. for the ASC4FIRST Investigators:
Asciminib in Newly Diagnosed Chronic Myeloid Leukemia.
N Engl J Med 2024;391:885-98.
DOI: 10.1056/NEJMoa2400858
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| wichtiger Hinweis! |
Eine Behandlung mit tumorwirksamen Medikamenten darf nur unter Aufsicht eines Arztes erfolgen, der über hinreichende Erfahrungen mit Tumoren und diesem Medikament hat. In Zweifelsfällen ist
die aktuelle Richtlinie und der Hersteller zu kontaktieren. |
|
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. Latest Updates Late Breaking Abstract-ASCO 2015:
Treating Cancer Based on Genomics Regardless of Tumor Type The FDA approves
IRESSA® for metastatic Non Small Cell Lung Cancer GILOTRIF® Superior to
TARCEVA® in Squamous Cell Carcinoma of the Lung Choosing Appropriate Therapy
in Chronic Myeloid Leukemia Radiation Therapy Added to Androgen Deprivation
Therapy Improves Overall Survival in Locally Advanced Prostate Cancer Fish
Oil and Certain Species of Fish May Negate the Effects of Chemotherapy
Unique Toxicities of Immunotherapy for the Clinician Tumor genomics May
Predict Outcomes with First Line Therapy in Metastatic Renal Cell Carcinoma
Late Breaking Abstract - ASCO 2015: IBRANCE® More Than Doubles Progression
Free Survival in Hormone Receptor Positive Advanced Breast Cancer Late
Breaking Abstract - ASCO 2015: Adjuvant Chemotherapy Improves Overall
Survival in Localized High Risk Prostate Cancer