Phase II clinical experience with the novel proteasome inhibitor bortezomib in patients with indolent non-Hodgkin's lymphoma and mantle cell lymphoma
Phase II clinical experience with the novel proteasome inhibitor bortezomib in patients with indolent non-Hodgkin's lymphoma and mantle cell lymphoma
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DOI：
10.1200/jco.2005.02.050
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发表时间：
2005-02-01
影响因子：
45.3
通讯作者：
Zelenetz, AD
中科院分区：
文献类型：
--
作者：
O'Connor, OA;Wright, J;Zelenetz, AD
目的研究新型蛋白酶体抑制剂硼替佐米对惰性和套细胞淋巴瘤（MCL）患者的抗肿瘤活性。在第1、4、8和11天给予硼替佐米1.5 mg/m2。要求患者接受不超过3种既往化疗方案，既往治疗后至少1个月，既往利妥昔单抗治疗后3个月，既往皮质类固醇治疗后7天;中性粒细胞绝对计数超过1，500/穆尔（500/穆尔，如果记录的骨髓受累）和血小板计数超过50，000/穆尔。滤泡性淋巴瘤10例，MCL 11例，小淋巴细胞性淋巴瘤（SLL）或慢性淋巴细胞性白血病（CLL）3例，边缘区淋巴瘤2例。总体缓解率为58%，其中1例完全缓解（CR），1例未经证实的CR（CRu），4例滤泡性非霍奇金淋巴瘤（NHL）患者部分缓解（PR）。所有反应都是持久的，持续时间为3至24+个月。1例MCL患者达到CRu，4例达到PR，4例病情稳定。1例MCL患者缓解19个月。两例边缘区淋巴瘤患者分别获得持续8+和11+个月的PR。SILL或CLL患者尚未作出反应。总体而言，该药物耐受性良好，仅发生1例4级毒性（低钠血症）。最常见的3级毒副反应为淋巴细胞减少（n = 14）和血小板减少（n = 7）。结论硼替佐米治疗某些亚型NHL患者耐受性好，单药疗效显著。
Purpose To determine the antitumor activity of the novel proteasome inhibitor bortezomib in patients with indolent and mantle-cell lymphoma (MCL).Patients and Methods Patients with indolent and MCL were eligible. Bortezomib was given at a dose of 1.5 mg/m(2) on days 1, 4, 8, and 11. Patients were required to have received no more than three prior chemotherapy regimens, with at least I month since the prior treatment, 3 months from prior rituximab, and 7 days from prior corticosteroids; absolute neutrophil count more than 1,500/muL (500/muL if documented bone marrow involvement); and platelet count more than 50,000/muL.Results Twenty-six patients were registered, of whom 24 were assessable. Ten patients had follicular lymphoma, 11 had MCL, three had small lymphocytic lymphoma (SLL) or chronic lymphocytic leukemia (CLL), and two had marginal zone lymphoma. The overall response rate was 58%, with one complete remission (CR), one unconfirmed CR (CRu), and four partial remissions (PR) among patients with follicular non-Hodgkin's lymphoma (NHL). All responses were durable, lasting from 3 to 24+ months. One patient with MCL achieved a CRu, four achieved a PR, and four had stable disease. One patient with MCL maintained his remission for 19 months. Both patients with marginal zone lymphoma achieved PR lasting 8+ and 11+ months, respectively. Patients with SILL or CLL have yet to respond. Overall, the drug was well tolerated, with only one grade 4 toxicity (hyponatremia). The most common grade 3 toxicities were lymphopenia (n = 14) and thrombocytopenia (n = 7).Conclusion These data suggest that bortezomib was well tolerated and has significant single-agent activity in patients with certain subtypes of NHL.