以硼替佐米为基础的联合方案治疗110例多发性骨髓瘤患者的疗效分析

Bortezomib-based regimen for the treatment of 110 multiple myeloma patients

目的 分析以硼替佐米为基础的联合方案治疗多发性骨髓瘤（MM）的临床疗效及不良反应.方法 选择2006年1月至2010年2月首都医科大学附属北京朝阳医院应用以硼替佐米为主的联合方案治疗的110例MM患者.年龄＞65岁的患者选用硼替佐米、地塞米松联合或不联合沙利度胺（PD±T）方案,或硼替佐米、马法兰、泼尼松（VMP）方案治疗;年龄≤65岁或对PD±T方案耐药的患者采用硼替佐米、多柔比星、地塞米松联合或不联合沙利度胺（PAD±T）方案治疗.回顾性分析治疗的临床疗效及不良反应.结果 110例患者中新诊断患者47例,复发/难治性患者63例.硼替佐米为基础的联合治疗方案总的有效（OR）率为76.4%（84/110）,其中新诊断患者优于复发/难治性患者（83.0%比71.4%,P＜0.05）.硼替佐米剂量对患者的完全缓解（CR）率与非常好的部分缓解（VGPR）率影响较大,硼替佐米1.0 mg/m2组患者CR＋VGPR率明显低于硼替佐米1.3 mg/m2组（新诊断患者：53.6%比73.7%;复发/难治性患者：28.9%比40.0%,均P＜0.05）.根据最新国际分期系统（ISS）,Ⅰ＋Ⅱ期患者疗效与Ⅲ期患者疗效差异无统计学意义（新诊断患者OR率：83.6%比82.1%;复发/难治性患者OR率：72.2%比69.2%,均P＞0.05）.新诊断患者中,有13例患者成功进行了自体干细胞移植,移植后均获得VGPR以上疗效,中位随访13.0个月（4.0～20.0个月）,2例患者髓外复发、治疗无效死亡,其余11例病情稳定.复发/难治性患者中,13例患者应用硼替佐米再治疗,CR率为15.4%（2/13）,VGPR率为23.1%（3/13）,部分缓解（PR）率为23.1%（3/13）,OR率为61.5%（8/13）,中位缓解持续时间（DOR）为6.7个月（3.0～21.0个月）.6例合并髓外浆细胞瘤的患者应用含硼替佐米方案治疗,所有患者均获得PR及以上疗效,中位DOR为4.5个月（2.0～10.0个月）.主要不良反应包括周围神经病变、血小板减少、粒细胞缺乏、乏力、胃肠道反应、贫血等.结论 硼替佐米为基础的治疗方案可以作为初治或复发/难治性MM患者的首选治疗.

Objective To analyze the outcomes and adverse effects of bortezomib-based regimen for the treatment of multiple myeloma （MM） patients. Methods A total of 110 MM patients were treated with a bortezomib-based regimen at our hospital from January 2006 to February 2010. The patients over 65 years old received bortezomib-prednisone ± thalidomide （PD ± T） regimen or velcade-melphalan-prednisone （VMP）regimen therapy and the patients under 65 years old or resistant to PD ± T regimen received bortezomibdoxorubicin-prednisone ± thalidomide （PAD ± T） regimen therapy. The outcomes and adverse effects of bortezomib-based regimen were retrospectively evaluated. Results There were 47 newly-diagnosed MM patients and 63 relapsing/refractory MM patients. The overall remission （OR） rate was 76. 4% （84/110）and the OR rate of newly-diagnosed MM patients was statistically higher than that of relapsing/refractory MM patients （83.0% vs 71.4%, P 〈0.05）. The complete remission（CR） ＋ very good partial remission （VGPR） rate in group bortezomib 1.0 mg/m2 was lower than that in group bortezomib 1.3 mg/m2 （newlydiagnosed 53. 6% vs 73.7%, relapsing/refractory 28. 9% vs 40. 0%, both P 〈0. 05）. The OR rate of ISS Ⅲ stage patients was as better as that of ISS Ⅰ and Ⅱ stage patients （newly-diagnosed 82. 1% vs 83.6%,relapsing/refractory 69. 2% vs 72. 2%, both P 〉 0. 05）. Thirteen newly-diagnosed MM patients underwent autologous stem cell transplantation （ASCT） after induced therapy and achieved a VGPR or above. The median follow-up time was 13.0 （6. 0 -20. 0）months. Their conditions were stable except two patients with extramedullary plasmacytoma after ASCT. Thirteen relapsing/refractory MM patients were retreated with a bortezomib-based regimen. The CR rate was 15.4% （2/13）, VGPR rate was 23.1% （3/13）, partial remission （PR） rate was 23. 1% （3/13）,OR rate 61.5% （8/13）and the median duration of remission （DOR） was 6. 7（3.0 -21.0） months. Six MM patients with extramedullary plasmacytoma were treated with a bortezomib-based regimen and all of them achieved a PR or above. The median DOR was 4.5 （2.0 -10.0） months. The main adverse effects were peripheral neuropathy, thrombocytopenia, neutropenia,fatigue, gastrointestinal symptoms, anemia, etc. Conclusion The bortezomib-based combination regimen is the front-line therapy for newly-diagnosed and relapsing/refractory MM patients.