伊布替尼治疗慢性淋巴细胞白血病的效果及安全性研究

Efficacy and safety of ibrutinib in treatment of chronic lymphocytic leukemia

目的探讨伊布替尼治疗慢性淋巴细胞白血病(CLL)的效果及安全性。方法回顾性分析1998年5月至2019年10月在福建医科大学附属协和医院确诊的68例CLL患者的临床资料,其中采用伊布替尼一线治疗39例,二线治疗20例,二线以上治疗9例。分析临床特征、IGHV基因突变及染色体核型分层患者近期疗效及生存情况,总结不良反应发生情况。结果随访截至2020年5月,中位随访时间53.2个月。伊布替尼治疗的客观缓解率(ORR)为83.8%(57/68),其中完全缓解8例(11.8%),部分缓解49例(72.1%),疾病稳定5例(7.4%),疾病进展6例(8.8%)。IGHV未突变患者ORR高于突变患者[93.3%(28/30)比76.3%(29/38),χ^(2)=33.656,P<0.05],国际预后指数(IPI)评分低危及低中危患者ORR高于中高危及高危者[90.6%(29/32)比77.8%(28/36),χ^(2)=7.248,P=0.007],其他因素分层患者间ORR差异均无统计学意义(均P>0.05)。68例患者中31例(45.6%)出现不良反应,均能坚持治疗;其中26例(38.2%)发生1~2级不良反应,5例(7.4%)发生3级及以上不良反应;因不良反应停药2例(2.9%)。全组患者的中位无进展生存(PFS)及总生存(OS)时间均未达到。伴有IGHV突变患者5年PFS率高于IGHV未突变者(100.0%比72.1%,P=0.020),染色体核型正常者5年PFS率高于染色体核型异常的患者(100.0%比74.3%,P=0.019)。结论伊布替尼治疗CLL具有良好的疗效和安全性。

Objective To investigate the clinical efficacy and safety of ibrutinib in treatment of chronic lymphocytic leukemia(CLL).Methods The clinical data of 68 patients with CLL in Fujian Medical University Union Hospital from May 1998 to October 2019 were retrospectively analyzed,including 39 cases receiving ibrutinib as the first therapy,20 cases receiving ibrutinib as the second therapy,and 9 cases receiving ibrutinib as the second and above therapy.The clinical characteristics,IGHV gene mutation,the short-term therapeutic efficacy and survival of patients with stratified chromosomal karyotype were analyzed;the adverse events were also analyzed.Results The median follow-up time was 53.2 months until May 2020.The objective remission rate(ORR)was 83.8%(57/68),including 8 cases(11.8%)of complete remission,49 cases(72.1%)of partial remission,5 cases(7.4%)of the stable disease,6 cases(8.8%)of progression of the disease.The ORR of patients without IGHVmutation was higher than that of those with IGHV mutation[93.3%(28/30)vs.76.3%(29/38),χ^(2)=33.656,P<0.05];the ORR of patients with low risk and low-moderate risk International Prognostic Index(IPI)score was higher than that of those with moderate-high risk and high risk[90.6%(29/32)vs.77.8%(28/36),χ^(2)=7.248,P=0.007],and differences in the ORR of patients stratified by other factors were not statistically significant(all P>0.05).Among 68 patients,31 cases(45.6%)had adverse reactions and they insistently received the treatment;26 cases(38.2%)had grade1-2 adverse reactions,5 cases(7.4%)had grade 3 and above adverse reactions;2 cases(2.9%)had drug withdrawal because of adverse reactions.The median progression-free survival(PFS)time and overall survival(OS)time of CLL patients treated with ibrutinib had not been reached.The 5-year PFS rate of patients with IGHV mutation was higher than that of patients with IGHV non-mutation(100.0%vs.72.1%,P=0.020),the 5-year PFS rate of patients with normal chromosome karyotype was higher than that of those with abnormal chromosome karyotype(100.0%vs.74.3%,P=0.019).Conclusion Ibrutinib is effective and safe in treatment of CLL patients.