Hypothesis: upfront use of ABL kinase inhibitor combination, either simultaneously or sequentially, in high-risk Ph+ leukemias?

A sequential treatment approach is the rule in CML and Ph(+) ALL with imatinib failure being followed by second-line tyrosine kinase inhibitors. The sequential strategy may be vulnerable to compound mutations. An alternative and fascinating hypothesis discussed in this paper is the upfront use, at least in very high-risk Ph(+) leukemias, of ABL kinase inhibitor combinations, either simultaneously or sequentially to target a wider range of mutations-based drug resistance. The main questions are: will TKI cocktails be able to eliminate the leukemic compartment? Which are the correct doses? Which are the long-term effects? Clinical trials have been recently initiated, and the future will give us the answer to all these questions.