Background: Bosutinib has a distinct adverse event (AE) profile vs other TKIs used to treat Ph+ leukemia. Methods: Pts with chronic phase (CP) chronic myeloid leukemia (CML; n=403) or accelerated/blast phase CML or Ph+ acute lymphoblastic leukemia (ADV; n=167) previously treated with imatinib ± dasatinib and/or nilotinib received bosutinib (starting dose 500 mg QD) in a phase 1/2 study (NCT00261846). Cross-intolerance (AEs leading to discontinuation of both prior TKI and bosutinib) and AEs causing prior TKI intolerance and recurring as grade 3/4 AEs with bosutinib were assessed after ≥4 y of follow-up. Results: In imatinib-intolerant and dasatinib-intolerant pts, respectively, 18% and 24% in the CP CML group and 18% and 5% in the ADV group had cross-intolerance with bosutinib, which was most commonly due to hematologic AEs (Table). Cross-intolerance in imatinib-intolerant pts with CP CML due to AEs common with imatinib was low (rash 6%; diarrhea 10%; edema/fluid retention 0; myalgia 0); cross-intolerance due to pleural effusion was low in dasatinib-intolerant pts with CP CML (13%) and dasatinib-intolerant ADV pts (0). No deaths occurred due to cross-intolerance. Conclusions: Cross-intolerance with bosutinib was low and largely due to hematologic AEs, supporting bosutinib use in pts with Ph+ leukemia intolerant to prior TKIs, including those with intolerance due to rash or diarrhea. Clinical trial information: NCT00261846

* Causes in ≥5 pts shown † Pts with known causes shown