Treatment recommendations based on BCR-ABL1 mutation profile...The table below lists the BCR-ABL1 mutations that should not be treated with bosutinib, dasatinib or nilotinib in the second-line setting...Bosutinib…T315I, V299L, G250E, or F317L

Responses were seen across Bcr-Abl mutations, including those associated with dasatinib and nilotinib resistance, except T315I. Bosutinib had an acceptable safety profile; treatment-emergent adverse events were primarily manageable grade 1/2 gastrointestinal events and rash. Grade 3/4 nonhematologic adverse events (> 2% of patients) included diarrhea (8%) and rash (4%). Bosutinib may offer a new treatment option for patients with chronic-phase CML after treatment with multiple TKIs. Table 4.....

CONTRADICTING EVIDENCE: Among the 115 patients with known mutations at baseline, the most common were M351T (n = 7), F359V (n = 7), F317L (n = 4), L248V (n = 4), G250E (n = 3), M244V (n = 3), and T315I (n = 3). Similar rates of CHR or MCyR were observed between patients with and without mutations. Responses were observed broadly across Bcr-Abl mutants, except for T315I (Figure 3 and supplemental Table 3).

In our study, we investigated the activity of bosutinib, dasatinib, imatinib, and nilotinib against a panel of 18 mutated forms of BCR/ABL associated with imatinib resistance in CML and Ph+ acute lymphoblastic leukemia patients. The results are listed in Figure 1 (Table 1 lists all the actual values for the relative concentration that inhibits 50%).