Myeloma Unit, Division of Hematology, University of Torino, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino, Torino, Italy.
Department of Clinical Oncology and Hematology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Clin Cancer Res. 2020 Sep 15;26(18):4832-4841. doi: 10.1158/1078-0432.CCR-20-0951. Epub 2020 Jul 2.
Duration of first remission is important for the survival of patients with multiple myeloma.
From the CoMMpass study (NCT01454297), 926 patients with newly diagnosed multiple myeloma, characterized by next-generation sequencing, were analyzed to evaluate those who experienced early progressive disease (PD; time to progression, TTP ≤18 months).
After a median follow-up of 39 months, early PD was detected in 191/926 (20.6%) patients, 228/926 (24.6%) patients had late PD (TTP >18 months), while 507/926 (54.8%) did not have PD at the current follow-up. Compared with patients with late PD, patients with early PD had a lower at least very good partial response rate (47% vs. 82%, < 0.001) and more frequently acquired double refractoriness to immunomodulatory drugs (IMiD) and proteasome inhibitors (PI; 21% vs. 8%, < 0.001). Patients with early PD were at higher risk of death compared with patients with late PD and no PD (HR, 3.65; 95% CI, 2.7-4.93; < 0.001), showing a dismal median overall survival (32.8 months). In a multivariate logistic regression model, independent factors increasing the early PD risk were mutation (OR, 3.78, < 0.001), high lactate dehydrogenase levels (OR, 3.15, = 0.006), λ-chain translocation (OR, 2.25, = 0.033), and mutation (OR, 2.15, = 0.007). Carfilzomib-based induction (OR, 0.15, = 0.014), autologous stem-cell transplantation (OR, 0.27, < 0.001), and continuous therapy with PIs and IMiDs (OR, 0.34, = 0.024) mitigated the risk of early PD.
Early PD identifies a high-risk multiple myeloma population. Further research is needed to better identify baseline features predicting early PD and the optimal treatment approaches for patients at risk.
首次缓解持续时间对多发性骨髓瘤患者的生存至关重要。
从 CoMMpass 研究（NCT01454297）中，分析了 926 例新诊断的多发性骨髓瘤患者，这些患者具有下一代测序特征，以评估那些经历早期进行性疾病（进展时间，TTP≤18 个月）的患者。
中位随访 39 个月后，在 926 例患者中检测到 191 例（20.6%）早期 PD，228 例（24.6%）患者出现晚期 PD（TTP>18 个月），而 507 例（54.8%）患者在当前随访中未发生 PD。与晚期 PD 患者相比，早期 PD 患者的至少非常好的部分缓解率较低（47% vs. 82%，<0.001），并且更频繁地对免疫调节剂（IMiD）和蛋白酶体抑制剂（PI）产生双重耐药性（21% vs. 8%，<0.001）。与晚期 PD 患者和无 PD 患者相比，早期 PD 患者的死亡风险更高（HR，3.65；95%CI，2.7-4.93；<0.001），中位总生存期较差（32.8 个月）。在多变量逻辑回归模型中，增加早期 PD 风险的独立因素是 突变（OR，3.78，<0.001）、高乳酸脱氢酶水平（OR，3.15，=0.006）、λ 链易位（OR，2.25，=0.033）和 突变（OR，2.15，=0.007）。卡非佐米为基础的诱导（OR，0.15，=0.014）、自体干细胞移植（OR，0.27，<0.001）和持续使用 PI 和 IMiD（OR，0.34，=0.024）可降低早期 PD 的风险。
早期 PD 可识别多发性骨髓瘤高危人群。需要进一步研究以更好地识别预测早期 PD 的基线特征和高危患者的最佳治疗方法。
