Markovic Uros, Romano Alessandra, Del Fabro Vittorio, Bellofiore Claudia, Bulla Anna, Parisi Marina Silvia, Leotta Salvatore, Gentile Massimo, Cangialosi Clotilde, Vincelli Iolanda, Mineo Giuseppe, Rossi Marco, Poidomani Massimo, Uccello Giuseppina, Maugeri Cinzia, Mannina Donato, Innao Vanessa, Di Raimondo Francesco, Conticello Concetta
Postgraduate School of Hematology, University of Catania, Catania, Italy.
Division of Hematology, University Hospital Policlinico Vittorio Emanuele, Catania, Italy.
Front Oncol. 2021 Mar 5;11:624405. doi: 10.3389/fonc.2021.624405. eCollection 2021.
The anti-CD38 monoclonal antibody daratumumab is approved as a single agent for the treatment of patients with relapsed/refractory multiple myeloma (RRMM) who received at least three prior lines of therapy, including proteasome inhibitor and immunomodulatory agent. A retrospective multicentric study was designed to evaluate feasibility, tolerability, and efficacy of daratumumab in monotherapy in RRMM.
This study included 44 consecutive RRMM patients that underwent daratumumab monotherapy after a median number of four prior therapies (range 2-9). Patients were treated in seven Sicilian centers, as part of Sicilian Myeloma Network and three Calabrian centers outside of controlled clinical trials from August 2016 through July 2020.
The regimen was well tolerated with few grade 3-4 haematological and rare non-haematological adverse events, such as pneumonia. Definitive discontinuation was due to disease progression in 25 (57%) patients. Since three patients did not complete at least one full cycle, a total of 41 patients was evaluated for response. Overall response rate was 37%, and the disease control rate (stable disease or better) was high (73%). The best achieved responses within 6 months were very good partial remission or better (27%), partial remission (10%), minimal response (14%) and stable disease (22%). After a median follow up of 7.8 months, median progression free survival (PFS) was 7.2 months and overall survival (OS) 7.8 months. Univariate analysis showed that patients with PR or better after 6 months of therapy had longer median PFS and OS (respectively 29.5 vs 3.6 months, p=0.0001 and 30.6 vs 3.9 months p=0.0001), confirmed by multivariate analysis. Furthermore, standard cytogenetic risk and biochemical relapse type had prolonged median PFS, but not OS (respectively unreached vs 2.6, p=0.03 and 23.9 vs 6.2, p=0.05) in both univariate and multivariate analysis. Additionally, univariate analysis showed that patients treated with carfilzomib-lenalidomide-dexamethasone prior to daratumumab had significantly shorter PFS compared to pomalidomide-dexamethasone (3.4 months vs 9.3 months, p=0.03), that multivariate analysis failed to confirm.
Our findings indicate that daratumumab as single agent is safe and well-tolerated regimen in real-life, associated to prolonged PFS and OS in responding patients. No new safety signals were identified.
抗CD38单克隆抗体达雷妥尤单抗被批准作为单药治疗复发/难治性多发性骨髓瘤（RRMM）患者，这些患者既往至少接受过包括蛋白酶体抑制剂和免疫调节剂在内的三线治疗。一项回顾性多中心研究旨在评估达雷妥尤单抗单药治疗RRMM的可行性、耐受性和疗效。
本研究纳入了44例连续的RRMM患者，他们在接受了中位数为4次（范围2 - 9次）的既往治疗后接受了达雷妥尤单抗单药治疗。作为西西里骨髓瘤网络的一部分，患者在西西里岛的7个中心以及2016年8月至2020年7月期间在卡拉布里亚的3个中心接受治疗，这些治疗均不属于对照临床试验。
该治疗方案耐受性良好，3 - 4级血液学不良事件较少，非血液学不良事件罕见，如肺炎。25例（57%）患者因疾病进展而最终停药。由于3例患者未完成至少一个完整周期，共有41例患者接受了疗效评估。总缓解率为37%，疾病控制率（病情稳定或更好）较高（73%）。6个月内达到的最佳缓解为非常好的部分缓解或更好（27%）、部分缓解（10%）、最小缓解（14%）和病情稳定（22%）。中位随访7.8个月后，中位无进展生存期（PFS）为7.2个月，总生存期（OS）为7.8个月。单因素分析显示，治疗6个月后达到PR或更好的患者中位PFS和OS更长（分别为29.5个月对3.6个月，p = 0.0001；30.6个月对3.9个月，p = 0.0001），多因素分析证实了这一点。此外，在单因素和多因素分析中，标准细胞遗传学风险和生化复发类型的中位PFS延长，但OS未延长（分别为未达到对2.6个月，p = 0.03；23.9个月对6.2个月，p = 0.05）。此外，单因素分析显示，在接受达雷妥尤单抗治疗之前接受卡非佐米 - 来那度胺 - 地塞米松治疗的患者与接受泊马度胺 - 地塞米松治疗的患者相比，PFS显著更短（3.4个月对9.3个月，p = 0.03），多因素分析未证实这一点。
我们的研究结果表明，在现实生活中，达雷妥尤单抗作为单药治疗是一种安全且耐受性良好的方案，与缓解患者的PFS和OS延长相关。未发现新的安全信号。
