Department of Translational and Precision Medicine, Azienda Ospedaliera Policlinico Umberto I, Sapienza University of Rome, Rome, Italy.
SSD Clinical Trials in Oncohematology and Multiple Myeloma, City of Health and Science University Hospital of Turin, Turin, Italy.
Hematology. 2024 Dec;29(1):2432815. doi: 10.1080/16078454.2024.2432815. Epub 2024 Nov 29.
Patients with multiple myeloma (MM) typically require multiple regimens and become harder to treat with each line of treatment. Furthermore, there is a lack of direct comparative clinical trial data to guide effective treatment sequencing. A novel model is described comparing alternative MM treatment sequences to optimize patient outcomes.
The model compares treatment sequences and outcomes for adults with newly diagnosed transplant-eligible (TE) or transplant-ineligible (TIE) MM across four treatment lines (first-line [FL] to fourth-line [4L]). Inputs are derived from patient-level data from clinical trials and indirect treatment comparisons. We report a base case prediction using data representing clinical practice in Italy.
For FL TE, overall survival (OS) and progression-free survival (PFS) were greatest for FL regimens containing daratumumab; OS ranged from 11.80-18.10 years. PFS ranged from 4.82-13.42 years (FL) to 0.66-6.03 years (second-line [2L]), 0.81-1.76 years (third-line [3L]), and 0.69-0.72 years (4L). For FL TIE, OS rates were greater for treatment sequences with FL daratumumab vs. sequences with either 2L or no daratumumab (OS ranging from 5.95-10.61 years). PFS was greatest for FL daratumumab regimens in the TIE group, with PFS ranging from 2.12-7.48 years (FL), 0.53-4.73 years (2L), 0.63-1.17 years (3L), and 0.42 years (4L).
This novel model demonstrates that using the most effective treatment in FL optimizes treatment sequencing and clinical outcomes for patients.
The optimal MM treatment sequences begin with daratumumab-containing regimens in FL and improve outcomes compared with alternative sequences.
多发性骨髓瘤（MM）患者通常需要多种治疗方案，且随着每一线治疗的进行，治疗难度也会加大。此外，缺乏直接的对照临床试验数据来指导有效的治疗排序。本研究描述了一种新的模型，旨在比较不同 MM 治疗方案的排列顺序，以优化患者结局。
该模型比较了四线（4L）治疗前具有适合移植（TE）或不适合移植（TIE）条件的新诊断 MM 成人患者的不同治疗方案和结局。输入数据来自临床试验和间接治疗比较的患者水平数据。我们报告了使用代表意大利临床实践数据的基本情况预测。
对于一线 TE 患者，含达雷妥尤单抗的一线治疗方案的总生存期（OS）和无进展生存期（PFS）最长；OS 范围为 11.80-18.10 年。PFS 范围为 4.82-13.42 年（一线）至 0.66-6.03 年（二线）、0.81-1.76 年（三线）和 0.69-0.72 年（四线）。对于一线 TIE 患者，含达雷妥尤单抗的治疗方案的 OS 率大于含二线或不含达雷妥尤单抗的治疗方案（OS 范围为 5.95-10.61 年）。TIE 组中达雷妥尤单抗一线治疗方案的 PFS 最长，PFS 范围为 2.12-7.48 年（一线）、0.53-4.73 年（二线）、0.63-1.17 年（三线）和 0.42 年（四线）。
该新型模型表明，在一线治疗中使用最有效的治疗药物可以优化患者的治疗排序和临床结局。
MM 的最佳治疗方案为一线治疗方案中包含达雷妥尤单抗，与其他方案相比，该方案可改善结局。
