Sagaster V, Ludwig H, Kaufmann H, Odelga V, Zojer N, Ackermann J, Küenburg E, Wieser R, Zielinski C, Drach J
Department of Internal Medicine I, Clinical Division of Oncology, Medical University of Vienna, Vienna, Austria.
Leukemia. 2007 Jan;21(1):164-8. doi: 10.1038/sj.leu.2404459. Epub 2006 Nov 9.
Studies of bortezomib in patients with relapsed multiple myeloma (MM) suggested that bortezomib may be active even in the presence of adverse prognostic factors. We therefore evaluated 62 patients with relapsed/refractory MM who were treated with single-agent bortezomib, and addressed the question whether or not the negative prognostic impact of unfavorable cytogenetic abnormalities may be overcome by bortezomib. By interphase fluorescence in situ hybridization (FISH), a deletion of chromosome 13q14 [del(13q14)] was present in 33 patients (53%). Overall response rates to bortezomib were similar in patients with and without del(13q14) (45 versus 55%; P=0.66), and rates of complete remission (CR) near CR were also not different between the two patient populations (18 versus 14%). Three patients had a t(4;14)(p16;q32) in addition to del(13q14), and all of them had a >50% paraprotein reduction. Median duration of response was 12.3 months in patients with del(13q14) compared with 9.3 months in patients with normal 13q-status (P=0.25), and survival was also not different between the two patient populations. Patients not benefiting from single-agent bortezomib were characterized by the combined presence of a del(13q14) and low serum albumin (median survival 4.6 months). Our results provide evidence for remarkable activity of bortezomib in MM with del(13q14). Patients who do not respond to bortezomib and consecutively have short time to treatment failure and overall survival can be identified by low serum albumin in addition to del(13q14) and should be considered for bortezomib combinations.
硼替佐米治疗复发多发性骨髓瘤(MM)患者的研究表明,即使存在不良预后因素,硼替佐米也可能具有活性。因此,我们评估了62例接受单药硼替佐米治疗的复发/难治性MM患者,并探讨了硼替佐米是否可以克服不良细胞遗传学异常的负面预后影响这一问题。通过间期荧光原位杂交(FISH)检测,33例患者(53%)存在13号染色体长臂14区缺失[del(13q14)]。有或无del(13q14)的患者对硼替佐米的总体缓解率相似(分别为45%和55%;P=0.66),两组患者的完全缓解(CR)及接近CR的比例也无差异(分别为18%和14%)。3例患者除del(13q14)外还存在t(4;14)(p16;q32),且所有患者的副蛋白降低均>50%。del(13q14)患者的中位缓解持续时间为12.3个月,而13q状态正常的患者为9.3个月(P=0.25),两组患者的生存率也无差异。未从单药硼替佐米治疗中获益的患者的特征为同时存在del(13q14)和低血清白蛋白(中位生存期4.6个月)。我们的结果为硼替佐米在伴有del(13q14)的MM中具有显著活性提供了证据。除del(13q14)外,血清白蛋白水平低可识别出对硼替佐米无反应、随后治疗失败时间短且总生存期短的患者,这些患者应考虑接受硼替佐米联合治疗。