Jaksic Wilfrid, Trudel Suzanne, Chang Hong, Trieu Young, Qi Xi, Mikhael Joseph, Reece Donna, Chen Christine, Stewart A Keith
Department of Medical Oncology and Hematology, Princess Margaret Hospital/University Health Network, University of Toronto, Toronto, Canada.
J Clin Oncol. 2005 Oct 1;23(28):7069-73. doi: 10.1200/JCO.2005.17.129. Epub 2005 Aug 29.
To determine whether primary drug resistance or rapid relapse explains the poor prognosis seen in t(4;14)-positive multiple myeloma (MM).
A total of 131 patients treated with high-dose therapy (HDT) were assessed, of whom 19 were t(4;14) positive. We examined the presentation features, chemotherapy responsiveness at presentation and to salvage therapies at relapse, and overall survival outcomes.
t(4;14)-positive patients had a predominance of the immunoglobulin A isotype (52.6%) but otherwise baseline characteristics were indistinguishable. After treatment with vincristine, doxorubicin, and dexamethasone or dexamethasone alone, 17 (89.7%) of the 19 patients achieved a partial response and 11 patients (57.9%) demonstrated an additional 50% reduction in paraprotein after HDT. Thus, t(4;14)-positive patients are chemotherapy sensitive; however, early progression was common, with 26% of patients progressing before HDT and a median progression-free survival after HDT of only 14.1 months. At relapse, a resistance to alkylating agents was evident, with no responses (zero of 11 patients) seen with conventional-dose alkylating agents. Salvage regimens using thalidomide and/or dexamethasone achieved at least minimal response in 59% of patients. The duration of response was short, however, with a median of only 4.7 months. The median overall survival after HDT was 24.2 months.
We conclude that t(4;14)-positive MM is chemotherapy sensitive but rapid relapse occurs. Resistance to alkylating agents is evident at relapse. The development of novel therapeutic agents is required, including the early clinical study of targeted fibroblast growth factor receptor 3 tyrosine kinase inhibitors, which have shown promise in preclinical studies.
确定原发性耐药或快速复发是否能解释t(4;14)阳性多发性骨髓瘤（MM）预后不良的情况。
对总共131例接受大剂量治疗（HDT）的患者进行评估，其中19例为t(4;14)阳性。我们研究了其临床表现特征、初诊时对化疗的反应以及复发时对挽救治疗的反应，还有总生存结果。
t(4;14)阳性患者中免疫球蛋白A亚型占主导（52.6%），但其他基线特征并无差异。在用长春新碱、阿霉素和地塞米松或仅用地塞米松治疗后，19例患者中有17例（89.7%）获得部分缓解，11例患者（57.9%）在HDT后副蛋白水平又降低了50%。因此，t(4;14)阳性患者对化疗敏感；然而，早期进展很常见，26%的患者在HDT前就进展，HDT后的无进展生存期（PFS）中位数仅为14.1个月。复发时，对烷化剂耐药明显，常规剂量烷化剂治疗无反应（11例患者中0例）。使用沙利度胺和/或地塞米松的挽救方案在59%的患者中至少达到了最小反应。然而，反应持续时间较短，中位数仅为4.7个月。HDT后的总生存期中位数为24.2个月。
我们得出结论，t(4;14)阳性MM对化疗敏感，但会快速复发。复发时对烷化剂耐药明显。需要开发新型治疗药物，包括对靶向成纤维细胞生长因子受体3酪氨酸激酶抑制剂进行早期临床研究，这类药物在临床前研究中已显示出前景。
