Department of Hematology, Amsterdam UMC, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, Amsterdam, the Netherlands.
HOVON Data Center, Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands.
J Clin Oncol. 2021 Sep 1;39(25):2758-2767. doi: 10.1200/JCO.20.03143. Epub 2021 May 4.
Frail patients with newly diagnosed multiple myeloma have an inferior outcome, mainly because of a high discontinuation rate due to toxicity. We designed a phase II trial specifically for frail patients, evaluating the efficacy and tolerability of ixazomib-daratumumab-low-dose-dexamethasone (Ixa-Dara-dex).
Sixty-five patients, who were frail according to the International Myeloma Working Group frailty index, were treated with nine induction cycles Ixa-Dara-dex followed by maintenance with Ixa-Dara for a maximum of 2 years.
The overall response rate on induction therapy was 78%. After a median follow-up of 22.9 months, median progression-free survival (PFS) was 13.8 months and 12-month overall survival (OS) was 78%. Median PFS and 12-month OS were 21.6 months and 92% in patients who were frail based on age > 80 years alone, versus 13.8 months and 78%, and 10.1 months and 70% in patients who were frail based on additional frailty parameters either ≤ 80 or > 80 years of age, respectively. In 51% of patients, induction therapy had to be discontinued prematurely, of which 6% because of noncompliance to study treatment, 9% because of toxicity, and 9% because of death (8% within 2 months, of which 80% because of toxicity). Quality of life improved during induction treatment, being clinically meaningful already after three induction cycles.
Ixa-Dara-dex lead to a high response rate and improved quality of life. However, treatment discontinuation because of toxicity and early mortality, negatively influencing PFS and OS, remains a concern in frail patients. The outcome was heterogeneous across frail subpopulations. This should be taken into account in the design and interpretation of future studies in frail patients, to pave the way for more precise treatment guidance.
新诊断多发性骨髓瘤的虚弱患者预后较差，主要是由于毒性导致停药率较高。我们专门为虚弱患者设计了一项 II 期试验，评估伊沙佐米-达雷妥尤单抗-低剂量地塞米松（Ixa-Dara-dex）的疗效和耐受性。
65 名根据国际骨髓瘤工作组虚弱指数判断为虚弱的患者接受了 9 个周期的 Ixa-Dara-dex 诱导治疗，随后接受 Ixa-Dara 维持治疗，最长达 2 年。
诱导治疗的总体缓解率为 78%。中位随访 22.9 个月后，中位无进展生存期（PFS）为 13.8 个月，12 个月总生存率（OS）为 78%。仅基于年龄＞80 岁的虚弱患者，中位 PFS 和 12 个月 OS 分别为 21.6 个月和 92%，而基于年龄≤80 岁或＞80 岁的其他虚弱参数的患者，分别为 13.8 个月和 78%，10.1 个月和 70%。51%的患者提前终止诱导治疗，其中 6%因不遵守研究治疗，9%因毒性，9%因死亡（2 个月内 8%，其中 80%因毒性）。诱导治疗期间生活质量得到改善，在接受三个诱导周期治疗后，生活质量已经具有临床意义。
Ixa-Dara-dex 可带来较高的缓解率和改善生活质量。然而，因毒性和早期死亡导致的治疗中断，对 PFS 和 OS 产生负面影响，仍是虚弱患者关注的问题。虚弱亚群之间的结果存在异质性。在未来的虚弱患者研究设计和解释中，应考虑这一点，为更精确的治疗指导铺平道路。
