Clinica di Ematologia Azienda Ospedaliero-Universitaria, Ospedali Riuniti di Ancona, Via Conca, 71, 60020, Ancona, Italy.
Ann Hematol. 2011 Dec;90(12):1449-56. doi: 10.1007/s00277-011-1217-0. Epub 2011 Mar 25.
In newly diagnosed multiple myeloma (MM), three/four-drug combinations as induction therapy seem to be more effective compared with two-drug associations in terms of response rate and duration of remission. Moreover, there is an emergent body of evidences that consolidation/maintenance therapy improves the quality of response and remission duration. However, the impact of these strategies in relapsed/refractory MM (r-rMM) is still unknown. This phase II study explored the four-drug combination of thalidomide, dexamethasone, pegylated liposomal doxorubicin (pLD), and bortezomib (ThaDD-V) as induction followed by consolidation therapy based on bortezomib-dexamethasone and thalidomide-dexamethasone and maintenance therapy with thalidomide in r-rMM patients. The primary end points of this study were best response and toxicity of the planned therapy. Forty-six patients were enrolled. At the end of therapy, the best response was as follows: 37% complete response (CR), 34.5% VGPR, and 4.5% PR with an ORR of 76%. Patients receiving ≤ 2 prior regimens had a CR rate significantly higher than those heavily treated (41% vs 0%; p=0.010). With a median follow-up of 31 months, median time to progression (TTP) and OS were 18.5 months and 40 months, respectively. By a 6-month landmark analysis, patients who completed the protocol had a significantly longer TTP compared with those who did not because of toxicity (not reached vs 7 months; p<0.0001). After the dose intensity of bortezomib was reduced due to an excess of peripheral neuropathy (PN), grade 3 PN occurred in 7.5% of patients. ThaDD-V followed by consolidation-maintenance therapy seems to be very effective in patients with r-rMM provided that this procedure is used early on relapse when very deep responses seem to be the rule.
在新诊断的多发性骨髓瘤（MM）中，与两药联合治疗相比，三/四药联合诱导治疗在缓解率和缓解持续时间方面似乎更有效。此外，越来越多的证据表明巩固/维持治疗可以提高缓解质量和缓解持续时间。然而，这些策略在复发/难治性 MM（r-rMM）中的影响仍不清楚。这项 II 期研究探讨了沙利度胺、地塞米松、聚乙二醇化脂质体阿霉素（pLD）和硼替佐米（ThaDD-V）的四联方案作为诱导治疗，随后进行硼替佐米-地塞米松巩固治疗和沙利度胺-地塞米松维持治疗，用于 r-rMM 患者。该研究的主要终点是计划治疗的最佳反应和毒性。共纳入 46 例患者。治疗结束时，最佳反应如下：完全缓解（CR）37%，非常好的部分缓解（VGPR）34.5%，部分缓解（PR）4.5%，总缓解率（ORR）为 76%。接受≤2 种既往方案治疗的患者的 CR 率显著高于接受多线治疗的患者（41% vs 0%；p=0.010）。中位随访 31 个月时，中位无进展生存期（TTP）和总生存期（OS）分别为 18.5 个月和 40 个月。通过 6 个月的时间点分析，由于毒性而未完成方案的患者的 TTP 明显短于完成方案的患者（未达到 vs 7 个月；p<0.0001）。由于周围神经病变（PN）过多，硼替佐米的剂量强度降低后，有 7.5%的患者发生 3 级 PN。在复发时尽早使用，当非常深的缓解似乎是常规时，ThaDD-V 序贯巩固维持治疗似乎对 r-rMM 患者非常有效。
