Department of Hematology, Vejle Hospital, Vejle, Denmark.
Department of Hematology, Herlev University Hospital, Herlev, Denmark.
PLoS One. 2021 Oct 13;16(10):e0258487. doi: 10.1371/journal.pone.0258487. eCollection 2021.
Most patients cannot be included in randomized clinical trials. We report real-world outcomes of all Danish patients with multiple myeloma (MM) treated with daratumumab-based regimens until 1 January 2019.
Information of 635 patients treated with daratumumab was collected retrospectively and included lines of therapy (LOT), hematologic responses according to the International Myeloma Working Group recommendations, time to next treatment (TNT) and the cause of discontinuation of treatment. Baseline characteristics were acquired from the validated Danish Multiple Myeloma Registry (DMMR).
Daratumumab was administrated as monotherapy (Da-mono) in 27.7%, in combination with immunomodulatory drugs (Da-IMiD) in 57.3%, in combination with proteasome inhibitors (Da-PI) in 11.2% and in other combinations (Da-other) in 3.8% of patients. The median number of lines of therapy given before daratumumab was 5 for Da-mono, 3 for Da-IMiD, 4 for Da-PI, and 2 for Da-other. In Da-mono, overall response rate (ORR) was 44.9% and median time to next treatment (mTNT) was 4.9 months. In Da-IMiD, ORR was 80.5%, and mTNT was 16.1 months. In Da-PI, OOR was 60.6% and mTNT was 5.3 months. In patients treated with Da-other, OOR was 54,2% and mTNT was 5.6 months. The use of daratumumab in early LOT was associated with longer TNT (p<0.0001). Patients with amplification 1q had outcome comparable to standard risk patients, while patients with t(4;14), t(14;16) or del17p had worse outcome (p = 0.0001). Multivariate analysis indicated that timing of treatment (timing of daratumumab in the sequence of all LOT that the patients received throughout the course of their disease) was the most important factor for outcome (p<0.0001).
The real-world outcomes of multiple myeloma patients treated with daratumumab are worse than the results of clinical trials. Outcomes achieved with daratumumab were best when daratumumab was used in combination with IMIDs and in early LOT. Patients with high-risk CA had worse outcomes, but patients with amp1q had similar outcomes to standard-risk patients.
大多数患者无法被纳入随机临床试验。我们报告了所有丹麦多发性骨髓瘤（MM）患者的真实世界结局，这些患者接受了达雷妥尤单抗为基础的治疗方案，直至 2019 年 1 月 1 日。
我们回顾性收集了 635 例接受达雷妥尤单抗治疗患者的数据，包括治疗线数（LOT）、根据国际骨髓瘤工作组建议的血液学反应、至下一治疗时间（TNT）和治疗终止的原因。基线特征来自经过验证的丹麦多发性骨髓瘤登记处（DMMR）。
达雷妥尤单抗单药治疗（Da-mono）占 27.7%，与免疫调节药物联合治疗（Da-IMiD）占 57.3%，与蛋白酶体抑制剂联合治疗（Da-PI）占 11.2%，与其他联合治疗（Da-other）占 3.8%。在 Da-mono 组中，中位数的治疗线数为 5 线，在 Da-IMiD 组中为 3 线，在 Da-PI 组中为 4 线，在 Da-other 组中为 2 线。在 Da-mono 组中，总体缓解率（ORR）为 44.9%，至下一治疗时间（mTNT）为 4.9 个月。在 Da-IMiD 组中，ORR 为 80.5%，mTNT 为 16.1 个月。在 Da-PI 组中，ORR 为 60.6%，mTNT 为 5.3 个月。在接受 Da-other 治疗的患者中，ORR 为 54.2%，mTNT 为 5.6 个月。在早期 LOT 中使用达雷妥尤单抗与更长的 TNT 相关（p<0.0001）。1q 扩增患者的结局与标准风险患者相当，而 t（4；14）、t（14；16）或 del17p 患者的结局更差（p=0.0001）。多变量分析表明，治疗时机（达雷妥尤单抗在患者整个疾病过程中接受的所有 LOT 序列中的治疗时机）是影响结局的最重要因素（p<0.0001）。
接受达雷妥尤单抗治疗的多发性骨髓瘤患者的真实世界结局比临床试验结果更差。达雷妥尤单抗联合 IMIDs 并在早期 LOT 中使用时，疗效最佳。高风险 CA 患者的结局更差，但 1q 扩增患者的结局与标准风险患者相似。
