Hematology Division, Università degli Studi di Torino, Turin, Italy.
Am J Hematol. 2013 Oct;88(10):838-42. doi: 10.1002/ajh.23501. Epub 2013 Jul 23.
Second generation tyrosine kinase-inhibitors (TKI) have been claimed to represent now the first-choice therapy for chronic myeloid leukemia (CML). Indeed, they generally induce faster and deeper molecular responses compared to imatinib that, however, is equally effective in at least 50% of patients. Moreover, some recent reports have questioned the long term safety of dasatinib and nilotinib. Therefore, upfront imatinib with early shift to second generation TKI for patients with slow/incomplete response might be as effective as front-line second generation TKI, with a possibly better safety profile. We retrospectively evaluated 91 chronic phase CML patients (median follow-up 57 months, median age 61 years), treated front-line with standard-dose imatinib and early therapy modifications (at 3-12 months) in case of unsatisfactory response or intolerance. Thirty-three patients (24 with unsatisfactory response, 9 intolerant) changed therapy, either by increasing imatinib dose (11/91) or by switching to second generation TKI (22 directly, 4 after high-dose imatinib). Globally, our strategy led to complete cytogenetic response (CCyR) in 98% of the patients, major molecular response (MMR) in 88% and molecular response 4 logs (MR(4.0) ) in 62%. Three patients in CCyR (3%), 2 of them in MMR too, suddenly progressed to blastic phase. At the last follow-up nine patients had died, seven of CML-unrelated causes and two only of CML progression. These results suggest that our strategy could be as effective as front line second generation TKI, with most of patients still receiving imatinib, a drug of better known long-term side effects and lower cost.
第二代酪氨酸激酶抑制剂（TKI）被认为是慢性髓性白血病（CML）的首选治疗药物。事实上，与伊马替尼相比，它们通常能更快、更深地诱导分子反应，而伊马替尼在至少 50%的患者中同样有效。此外，一些最近的报告质疑达沙替尼和尼洛替尼的长期安全性。因此，对于反应缓慢/不完全的患者， upfront 伊马替尼早期转为第二代 TKI 可能与一线第二代 TKI 同样有效，且安全性可能更好。我们回顾性评估了 91 例慢性期 CML 患者（中位随访时间为 57 个月，中位年龄为 61 岁），一线使用标准剂量伊马替尼治疗，并在反应不佳或不耐受时早期进行治疗调整（3-12 个月）。33 例患者（24 例反应不佳，9 例不耐受）改变了治疗方案，要么增加伊马替尼剂量（91 例中有 11 例），要么改用第二代 TKI（22 例直接转换，4 例在高剂量伊马替尼治疗后转换）。总体而言，我们的策略使 98%的患者达到完全细胞遗传学缓解（CCyR），88%达到主要分子缓解（MMR），62%达到分子反应 4 对数（MR(4.0)）。在 CCyR 中有 3 例（3%）患者、2 例在 MMR 中也突然进展为急变期。在最后一次随访时，有 9 例患者死亡，7 例与 CML 无关，2 例仅与 CML 进展有关。这些结果表明，我们的策略可能与一线第二代 TKI 同样有效，大多数患者仍在接受伊马替尼治疗，伊马替尼的长期副作用和成本都较低。
