PAD方案治疗初治多发性骨髓瘤的临床疗效

Clinical efficacy of PAD chemotherapy in patients with newly diagnosed multiple myeloma

目的:评估PAD方案(硼替佐米+脂质体多柔比星+地塞米松)治疗初治多发性骨髓瘤(MM)的疗效和安全性。方法:初治MM 27例,均给予PAD方案为一线治疗:硼替佐米1.3mg/m2,静脉注射,第1、4、8、11天;脂质体多柔比星20mg,静脉滴注,第1、4、8天;地塞米松20~40mg/d,静脉滴注,第1、4、8、11天;每28d为1个周期。27例患者接受平均4(2~8)个疗程的治疗。观察其短期疗效和长期疗效,并判断其不良反应。结果:近期疗效观察:初始疗效的中位时间为2周,最佳疗效的中位时间为3个月。总反应率为89%,其中完全缓解14例(52%),非常好的部分缓解2例(7%),部分缓解8例(30%)。此外,疾病稳定3例(11%),疾病控制100%。长期疗效观察:中位随访49(7~96)个月,中位无进展生存时间24个月,中位生存时间50个月。患者3年、5年、7年的无疾病进展率分别为37.0%、17.3%和8.6%,3年、5年、7年的总生存率分别为51.9%、47.9%和47.9%。主要的不良反应为血液学毒性,中性粒细胞减少8例(30%),贫血5例(19%),血小板减少7例(26%)。非血液学毒性主要为胃肠道症状,便秘10例(37%),腹泻、恶心、黏膜炎分别为2例(7%);其次为周围神经病变,1/2级7例(26%),3级2例(7%)。4例(15%)出现手足综合征,4例(15%)出现乏力,2例(7%)肝功能异常,2例(7%)并发带状疱疹。结论:PAD方案对于初治MM总反应率高,起效快,不良反应较小,是一种安全、有效的治疗方法。其长期疗效显示,PAD方案能使MM获得最大程度的缓解,适当的维持治疗后近半数患者长期生存。

Objective：To evaluate the efficacy and safety induced by PAD （bortezomib ＋ pegylated liposomal doxorubicin ＋ dexamethasone） regimen in patients with newly diagnosed multiple myeloma （MM）. Method： Twenty-seven patients with newly diagnosed MM were treated with PAD regimen as first line therapy： bortezomib 1.3 mg/m^2 intravenous injection on day 1,4,8,11 ;pegylated liposomal doxorubicin 20 mg intravenously on day 1, 4,8;dexamethasone 20 to 40 mg intravenously on day 1,4,8,11. The chemotherapy was repeated every 28 days as a course. The patients were applied 4（2 to 8） courses of treatment. The short-term efficacy,long-term efficacy and the toxicity of PAD regimen were analyzed. Result： The median time to initial response was 2 weeks and the median time to best response was 3 months. The overall clinical response was observed in 89 ~ patients,including complete response in 14（52%） patients,very good partial response in 2（7%） patients,partial response in 8（30%） patients, and stable disease in 3 （11%） patients. The disease control rate was 100%. After 49 （7 to 96） months of median follow-up,the median time of progression-free survival （PFS） was 24 months, and the median survival was 50 months. The 3-year, 5-year and 7-year PFS was 37.0 %, 17.3% and 8.6 %, respectively. And the 3-year, 5-year and 7-year overall survival was 51.9 %, 47.9% and 47.9%, respectively. The major adverse events were hematologic toxicity,including neutropenia （8 patients, 30 % ）, anemia （ 5 patients, 19 %） and thrombocytopenia （ 7 patients, 26%）. The most common non-hematologic toxicity were gastrointestinal symptoms, including constipation in 10 （37 % ） patients, diarrhea in 2 （7% ） patients, nausea in 2 （7%） patients and mucositis in 2 （7%） patients. Other non-hematologic toxicity were peripheral neuropathy [grade 1/2 in 7 （26%） patients and grade 3 in 2 （7%） patients], hand-foot syndrome in 4 （15%） patients, fatigue in 4 （15 0%） patients, liver function abnormal in 2 （7% ） patients,and herpes zoster in 2 （7 %） patients. Conclusion：PAD scheme is an effective therapy with a high response rate and manageable toxicities for patients with newly diagnosed MM. PAD can achieve utmost remission, nearlyhalf of the patients remain long-term survival after suitable maintenance.