State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Tianjin, China.
Division of Hematology, Oncology, and Blood and Marrow Transplantation, Department of Internal Medicine, University of Iowa, Iowa City, IA.
Blood Adv. 2019 Oct 8;3(19):2895-2904. doi: 10.1182/bloodadvances.2019000432.
Rapid remission by induction therapy has long been recognized as an important predictor for long-time survival in acute leukemia. However, the impact of response kinetics on multiple myeloma (MM) seems to be different and remains unexplored. The relationship between response kinetics and outcome were assessed in 626 patients with newly diagnosed MM who were included in a prospective, nonrandomized clinical trial (BDH 2008/02). Patients were assigned to either immunomodulatory drug- or proteasome inhibitor-based therapy. The response depth, time to best response (T) and duration of best response (D) were collected. Depth of response was associated with superior outcomes, consistent with findings from other studies. However, the early responders (defined as T ≤3 months) showed significantly worse survival compared with late responders. We found that patients with rapid complete remission experienced inferior survivals comparable to those attaining a gradual partial remission. Moreover, 4 distinct response kinetics patterns were identified. Patients with gradual and sustained remission ("U-valley" pattern) experienced superior outcomes, whereas poor outcomes were observed in rapid and transient responders ("roller coaster" pattern) (median overall survival, 126 vs 30 months). The effects of response patterns on survival were confirmed in patients at different stages of disease and cytogenetic risk, including transplant-eligible patients and those attaining different extents of response depth. Collectively, our data indicated that slow and gradual response is a favorable prognostic factor in MM. In addition to response depth, the kinetic pattern of response is a simple and powerful predictor for survival even in the era of novel agents.
诱导治疗的快速缓解长期以来一直被认为是急性白血病长期生存的重要预测因素。然而，反应动力学对多发性骨髓瘤（MM）的影响似乎不同，仍有待探索。在一项前瞻性、非随机临床试验（BDH 2008/02）中，对 626 例新诊断为 MM 的患者评估了反应动力学与结局之间的关系。患者被分配到免疫调节剂药物或蛋白酶体抑制剂为基础的治疗。收集了反应深度、最佳反应时间（T）和最佳反应持续时间（D）。反应深度与较好的结局相关，这与其他研究的发现一致。然而，早期反应者（定义为 T ≤3 个月）的生存明显差于晚期反应者。我们发现，快速完全缓解的患者的生存情况与逐渐部分缓解的患者相当，且生存情况较差。此外，还发现了 4 种不同的反应动力学模式。缓慢且持续缓解的患者（“U 型谷”模式）的结局较好，而快速且短暂缓解的患者（“过山车”模式）的结局较差（中位总生存期，126 个月与 30 个月）。在不同疾病阶段和细胞遗传学风险的患者中，包括适合移植的患者和达到不同反应深度的患者中，均证实了反应模式对生存的影响。综上所述，我们的数据表明，在 MM 中，缓慢而逐渐的反应是一个有利的预后因素。除了反应深度外，反应动力学模式即使在新型药物时代也是一个简单而强大的生存预测因素。
