Gleevec is the most commonly used medication for people with CML starting treatment with a TKI (tyrosine kinase inhibitor), and regular blood tests indicate if the person is responding to the medication. The type of response will change during the course of treatment according to the different milestones that have been established (see What is a “response”? CML-IQ, February 19, 2015.)
But what if Gleevec doesn’t produce a good enough response?
Fortunately, there are two good options – either increasing the dose of Gleevec, or switching to one of the second-generation TKIs (Tasigna, Sprycel or Bosulif).
Both of these approaches were examined in the TIDEL-II study (Yeung and colleagues. Blood 2015;125:915-923). (TIDEL stands for Therapeutic Intensification in De Novo Leukaemia.)
The TIDEL-I study had previously shown that starting with a higher dose of Gleevec early on could be beneficial (Hughes and colleagues. Blood 2008;112:3965-3973). So a higher starting dose of Gleevec (600 mg per day) was used in TIDEL-II. Treatment was considered to have failed if people didn’t reach key response milestones: a 1-log reduction in BCR-ABL transcripts at three months, a 2-log reduction at six months, or a 3-log reduction at 12 months. If one of these targets was missed, the dose of Gleevec was increased to 800 mg per day, or the person was switched to Tasigna. People in the high-dose Gleevec group were switched to Tasigna later on if their response continued to be poor.
Over the course of two years, about one-third of people took Tasigna and the rest had an adequate response to higher doses of Gleevec. For the group as a whole, a major molecular response (MMR, i.e. a 3-log reduction) was achieved by 64% after one year, and 73% after two years of treatment. One-third achieved a 4.5-log reduction. Overall survival at three years was 96%.
So this strategy of either increasing the dose of Gleevec or switching to a second-generation TKI appears to be highly successfully in optimizing a person’s response to treatment.