The association between multiple mutations and response to second-line kinase inhibitor therapy. Among the 220 imatinib-resistant CML patients analyzed for BCR-ABL1 kinase domain mutations by sequencing and mass spectrometry before commencing nilotinib/dasatinib therapy (switchover), 175 did not have detectable mutations known to confer clinical resistance to the inhibitor they received. Patients were categorized on the basis of the presence (n = 34) or absence (n = 141) of multiple sensitive mutations detected by mass spectrometry at switchover. (A) Cumulative incidence of CCyR and/or its equivalent of ≤ 1% BCR-ABL1 IS (International Scale),²⁶  according to disease phase at switchover. (B) Cumulative incidence of major molecular response (MMR; ≤ 0.1% BCR-ABL1 IS), according to disease phase at switchover. (C) Rate of new resistant mutations detected by direct sequencing during nilotinib/dasatinib therapy, according to disease phase at switchover.