The Average Baseline BCR-ABL Levels Are Significantly Higher in Patients with Resistance to Dasatinib As First-Line Treatment for Early Chronic Phase Chronic Myeloid Leukemia

The development of drug resistance remains a problem for some chronic myeloid leukemia (CML) patients treated with tyrosine kinase. Point mutations are the main mechanism behind drug resistance, and they can occur prior to therapy. Thus, there may be a positive correlation between the baseline BCR-ABL levels and the occurrence of drug resistance.

We define a “relapse/no-response” as a BCR-ABL/ABL transcript ratio of >10% (international scale) at 6 months or later during continuous dasatinib treatment. Statistical analysis is performed an all early chronic phase CML treated with dasatinib as first-line therapy (n=102) in a prospective clinical trial at the M.D. Anderson Cancer Center. The probability of having drug resistant leukemic cells already present at diagnosis is also estimated.

Seven of the 90 (7.8%) evaluable patients had a “relapse/no-response”. The mean (median) BCR-ABL/ABL transcript ratio at baseline for the “relapse/no-response” group was 23.3% (20.7%), while for the rest of the patients was 14.1% (9.9%), a statistically significant difference. The incidence rates of “relapse/no-response” for patients with a BCR-ABL/ABL transcript ratio at baseline equal to or larger than 20% was 13.8%, versus 7.8% overall for the entire dataset. Our estimates suggest that if the therapy were to be started on average one month earlier, the probability of a “relapse/no-response” would decrease from 7.8% to 6.9%.

The BCR-ABL transcript levels at baseline are significantly higher for those patients later incurring in a “relapse/no-response”. Moreover, our estimates suggest that starting the treatment as soon as possible after diagnosis may be critical for reducing the number of patients developing drug resistance.

Kantarjian:Novartis: Research Funding; Pfizer: Research Funding; Ariad: Research Funding; Bristol-Myers Squibb: Research Funding. Jabbour:Pfizer: Honoraria; Novartis: Honoraria; BMS: Honoraria. Cortes:Novartis: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Ariad: Consultancy, Research Funding.