Imatinib Intolerance Is Associated With Blastic Phase Development in Philadelphia Chromosome–Positive Chronic Myeloid Leukemia

Abstract Background Over the past years, the survival of patients with Philadelphia-positive chronic myeloid leukemia (CML Ph + ) has increased as a result of therapy with tyrosin kinase inhibitors (TKIs). Intolerance to TKIs has been described in approximately 20% of patients receiving treatment. We studied the incidence of imatinib intolerance in patients with CML Ph + and their outcome in our CML reference site, as there is no information about the evolution of patients intolerant to TKIs. Patients and Methods A group of 86 patients with CML Ph + receiving imatinib monotherapy who abandoned treatment were the basis for this study. We present the trends of their disease evolution. Results The median of age at diagnosis was 42 years. Within a year, 19 (22%) of 86 patients developed imatinib intolerance, all of them with grade III or IV disease that required imatinib dose reduction or discontinuation. Of these patients, 16 (84%) of 19 developed transformation to blastic phase. The cumulative incidences of blastic phase development were 47% in the nonintolerant group and 84% in the intolerant group. There was a relative risk for those with imatinib intolerance to develop blastic phase of 1.78 (95% confidence interval, 1.28 to 2.42) ( P Conclusion Most imatinib-intolerant patients develop blastic phase transformation, with a poor survival of 3 to 6 months; no effective rescue treatment is available. Future research should to determine whether the origin of this evolution is really due to the intolerance itself or whether it is due to a more aggressive form of the disease, perhaps related to genetic transformation.