Final analysis of the efficacy and safety of omacetaxine mepesuccinate in patients with chronic- or accelerated-phase chronic myeloid leukemia: Results with 24 months of follow-up.
Final analysis of the efficacy and safety of omacetaxine mepesuccinate in patients with chronic- or accelerated-phase chronic myeloid leukemia: Results with 24 months of follow-up.
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DOI：
10.1002/cncr.29240
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发表时间：
2015-05-15
期刊：
影响因子：
6.2
通讯作者：
Nicolini FE
中科院分区：
文献类型：
--
作者：
Cortes JE;Kantarjian HM;Rea D;Wetzler M;Lipton JH;Akard L;Khoury HJ;Michallet M;Guerci-Bresler A;Chuah C;Hellmann A;Digumarti R;Parikh PM;Legros L;Warzocha K;Baccarani M;Li E;Munteanu M;Nicolini FE
Omacetaxine是一种蛋白质合成抑制剂，在美国适用于治疗对两种或多种酪氨酸激酶抑制剂耐药和/或不耐受的慢性（CP）或加速期（AP）慢性髓性白血病（CML）患者。该最终分析（24个月随访）包括额外的疗效和安全性分析，以评估长期omacetaxine给药（1.25 mg/m2 bid，14天q28天，随后7天q28天）在接受>3个周期的CP-和AP-CML患者中的获益。18%的CP-CML患者达到主要细胞遗传学缓解（MCyR），中位持续时间为12.5个月（95%置信区间[CI]，3.5-未达到[NR]）; 14例缓解者中有3例的缓解维持≥12个月，中位总生存期（OS）为40.3个月（95% CI，23.8-未达到）。在AP-CML患者中，14%达到或维持主要血液学缓解的中位时间为4.7个月（95% CI，3.6-NR）;未达到MCyR，中位OS为14.3个月（95% CI，6.7-18.7）。在接受>3个周期治疗的CP-或AP-CML患者中（分别为n=50和14），中位OS分别为49.3个月（95%CI，23.8-NR）和24.6个月（95%CI，12-37.2）。≥3级血液学毒性是主要副作用（CP-CML/AP-CML中79%/73%），10%的CP和5%的AP患者因毒性而停药。这些结果表明，通过剂量调整来管理毒性，长期给予omacetaxine是可行的，并且omacetaxine在某些患者中提供了持久的获益。
Omacetaxine, a protein synthesis inhibitor, is indicated in the US for the treatment of patients with chronic (CP) or accelerated phase (AP) chronic myeloid leukemia (CML) with resistance and/or intolerance to two or more tyrosine kinase inhibitors. This final analysis, with 24-month follow-up, includes additional efficacy and safety analyses to assess the benefit of long-term omacetaxine administration (1.25 mg/m2 bid for 14 days q 28 days followed by 7 days q 28 days) in CP- and AP-CML patients receiving >3 cycles. Eighteen percent of CP-CML patients achieved major cytogenetic response (MCyR) with a median duration 12.5 months (95% confidence interval [CI], 3.5-not reached [NR]); responses were maintained for ≥12 months in 3 of 14 responders and median overall survival (OS) was 40.3 months (95% CI, 23.8-not reached). In patients with AP-CML, 14% achieved or maintained major hematologic response for a median of 4.7 months (95% CI, 3.6-NR); MCyR was not achieved and median OS was 14.3 months (95% CI, 6.7–18.7). In patients with CP- or AP-CML who received >3 cycles of treatment (n=50 and 14, respectively), median OS was 49.3 months (95% CI, 23.8-NR) and 24.6 months (95% CI, 12–37.2), respectively. Grade ≥3 hematologic toxicity was the major side effect (79%/73% in CP-CML/AP-CML), with discontinuation due to toxicity in 10% of CP and 5% of AP patients. These results suggest that long-term administration of omacetaxine is feasible with dose adjustments to manage toxicities, and that omacetaxine provides durable benefit in some patients.
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