Therapy of Early Chronic Phase Chronic Myeloid Leukemia (CML-CP) with Lower Dose Dasatinib
Dasatinib is a potent tyrosine kinase inhibitor (TKI) of BCR-ABL. Approved dose in the chronic phase is 100mg daily. This is however associated with notable side effects mainly myelosuppression and pleural effusion, leading to dose reductions/interruptions.
BCR-ABL1 tyrosine kinase inhibitors have dramatically improved outcomes for patients with chronic myeloid leukemia, and current studies are investigating whether some patients may be able to suspend therapy yet maintain response in a state known as “treatment-free remission” (TFR). Results from ongoing studies suggest that ≈ 40% to 60% of patients in sustained (generally ≥ 2 years) deep molecular response (defined as a 4-log or deeper reduction in BCR-ABL1 transcripts, depending on the study) who attempt TFR may successfully remain off treatment.
Conditions: Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Acute Leukemia in Remission; Acute Lymphoblastic Leukemia; Acute Myeloid Leukemia; Acute Myeloid Leukemia With FLT3/ITD Mutation; Acute Myeloid Leukemia With Gene Mutations; Aplastic Anemia; B-Cell Non-Hodgkin Lymphoma; CD40 Ligand Deficiency; Chronic Granulomatous Disease; Chronic Leukemia in Remission; Chronic Lymphocytic&n...
Publication date: October 2017 Source:Clinical Lymphoma Myeloma and Leukemia, Volume 17, Issue 10, Supplement Author(s): Michael J. Mauro, Jorge E. Cortes, Andreas Hochhaus, Neil P. Shah, Ehab Atallah, Mena Abaskharoun, Oumar Sy, Giuseppe Saglio
Publication date: October 2017 Source:Clinical Lymphoma Myeloma and Leukemia, Volume 17, Issue 10, Supplement Author(s): Kiran Naqvi, Jorge Cortes, Jeffrey Skinner, Elias Jabbour, Naveen Pemmaraju, Gautam Borthakur, Zeev Estrov, Prithviraj Bose, Philip Thompson, Hagop Kantarjian
Publication date: October 2017 Source:Clinical Lymphoma Myeloma and Leukemia, Volume 17, Issue 10, Supplement Author(s): Hee-Je Kim, Hea-Lyun Yoo, Won-Sik Lee, Hyeong-Joon Kim, Jee Hyun Kong, Yunsuk Choi, Young Rok Do, Jae-Yong Kwak, Sukjoong Oh, Sung Hyun Kim, Jeong-A. Kim, Dae Young Zang, Yeung-Chul Mun, Young-Woong Won, Sung-Eun Lee, Dong-Wook Kim
Although failure to achieve molecular response milestones on tyrosine kinase inhibitors (TKIs) therapy for chronic phase (CP) chronic myeloid leukemia (CML) means that switching to a different TKI is needed to limit the risk of progression and death, there is insufficient data to show long-term outcomes in the patients who were in a molecular failure after 24 months.
Treatment choice can be affected by patient comorbidities. Retrospective analysis of the phase 3 DASISION study suggested baseline comorbidities did not substantially affect 1-year safety and efficacy.
In conclusion, this retrospective analysis shows that IM can be safely and effectively administered following optimal response to 2G-TKIs. A prospective trial exploring this approach is currently enrolling and will be needed to confirm the safety and efficacy of this therapeutic approach.