Chronic myelogenous leukemia is now routinely treated with a tyrosine kinase inhibitor (TKI), a family of drugs that blocks leukemia signalling in the bone marrow and arrests the disease process. Three TKIs are approved for use in people newly diagnosed with chronic-phase CML: Gleevec (imatinib), which was the first TKI developed; and the second-generation TKIs Sprycel (dasatinib) and Tasigna (nilotinib).
How do these three medications compare?
The MD Anderson Cancer Center in Houston, Texas, analysed 487 people starting treatment with one of these drugs to compare how well they did (Jain and colleagues. Br J Haematol 2016;173:114-126). The benchmarks for treatment success were those developed by the European LeukemiaNet group (Baccarani and colleagues. Blood 2013;122:872-884). According to those recommendations, an optimal response is a 1-log reduction or better in BCR-ABL transcripts at three months, a 2-log reduction or better at 6 months, and a 3-log reduction or better at 12 months. (BCR-ABL transcripts are the signalling molecules produced by the CML cancer gene, BCR-ABL. A “log reduction” means that the number of molecules is reduced by a factor of 10: 100% reduced to 10% is a 1-log reduction, 100% reduced to 1% would be a 2-log reduction, and so on.)
Overall, people were more likely to achieve the 3-month benchmark if they took Tasigna (97%) or Sprycel (89%) or high-dose Gleevec (90%) compared to the usual dose of Gleevec (75%). (A higher dose of Gleevec was more common as an option before second-generation TKIs were developed.)
At six months, 89% of people on Tasigna, 86% on Sprycel, and 80% on high-dose Gleevec reached their treatment targets, compared to 41% on regular-dose Gleevec. The treatment success rate continued to be higher after 12 months on therapy with Tasigna (87%) compared to Sprycel (76%), and the two doses of Gleevec (77%; 47%).
Optimal these response milestones was important because they were reliable predictors of who was less likely to suffer a relapse, and who was more likely to survive. These findings also underscore the importance of regular testing to ensure that you are responding well to your medication and maintaining control over your CML.