Musto Pellegrino, Rossini Fausto, Gay Francesca, Pitini Vincenzo, Guglielmelli Tommasina, D'Arena Giovanni, Ferrara Felicetto, Filardi Nunzio, Guariglia Roberto, Palumbo Antonio
Unit of Hematology and Stem Cell Transplantation, CROB-Reference Cancer Center of Basilicata, Rionero in Vulture (Pz), Italy.
Cancer. 2007 Jun 1;109(11):2285-90. doi: 10.1002/cncr.22700.
The prognosis of patients with plasma cell leukemia (PCL), an aggressive variant of multiple myeloma (MM), is usually poor. Bortezomib is the first proteasome inhibitor approved for the treatment of advanced MM. Currently available information regarding the role of bortezomib in PCL is scanty and derives from anecdotal, single-case reports.
The authors conducted a retrospective survey of unselected Italian patients with primary or secondary PCL who were treated with bortezomib outside of clinical trials. Twelve evaluable patients were recorded who had received bortezomib for 1 to 6 cycles as either a single agent or variously combined with other drugs. Three patients were treated with bortezomib as frontline therapy, and 9 patients received bortezomib after 1 to 4 lines of chemotherapy, including autologous stem cell transplantation and thalidomide.
According to the International uniform response criteria of the International Myeloma Working Group, 5 partial responses (defined as a reduction in M-protein of >50%), 4 very good partial responses (defined as a reduction of >90% in M-protein), and 2 complete responses (defined as negative immunofixation) were achieved, for a response rate of 92%. Responses did not appear to be influenced by previous treatments or by other clinical or biologic parameters, including chromosome 13 deletion or the combination of bortezomib with other drugs. The median progression-free and overall survivals after bortezomib were 8 months and 12 months, respectively. At the time of last follow-up, 8 patients were alive 6 to 21 months after treatment with bortezomib, 4 of whom were in very good partial or complete responses. Grade 3/4 hematologic or neurologic toxicities (graded according to the Common Terminology Criteria for Adverse Events [CTCAE; version 3]) were reported to occur in 9 patients and 1 patient, respectively, whereas 6 patients experienced possible or documented infections.
Bortezomib appears to be an effective drug for PCL that could significantly improve the usually adverse clinical outcome of these patients.
浆细胞白血病（PCL）是多发性骨髓瘤（MM）的一种侵袭性变异型，其患者的预后通常较差。硼替佐米是首个被批准用于治疗晚期MM的蛋白酶体抑制剂。目前关于硼替佐米在PCL中作用的可用信息较少，且多来自轶事性的单病例报告。
作者对在临床试验之外接受硼替佐米治疗的未经选择的意大利原发性或继发性PCL患者进行了一项回顾性调查。记录了12例可评估患者，他们接受了1至6个周期的硼替佐米治疗，硼替佐米作为单一药物或与其他药物联合使用。3例患者接受硼替佐米作为一线治疗，9例患者在接受1至4线化疗（包括自体干细胞移植和沙利度胺）后接受硼替佐米治疗。
根据国际骨髓瘤工作组的国际统一反应标准，获得了5例部分缓解（定义为M蛋白降低>50%）、4例非常好的部分缓解（定义为M蛋白降低>90%）和2例完全缓解（定义为免疫固定阴性），缓解率为92%。缓解似乎不受既往治疗或其他临床或生物学参数的影响，包括13号染色体缺失或硼替佐米与其他药物的联合使用。硼替佐米治疗后的无进展生存期和总生存期的中位数分别为8个月和12个月。在最后一次随访时，8例患者在接受硼替佐米治疗后6至21个月仍存活，其中4例处于非常好的部分缓解或完全缓解状态。分别有9例和1例患者报告发生3/4级血液学或神经毒性（根据不良事件通用术语标准[CTCAE；第3版]分级），而6例患者经历了可能或有记录的感染。
硼替佐米似乎是一种治疗PCL的有效药物，可显著改善这些患者通常不良的临床结局。
