Gil-Sierra Manuel David, Briceño-Casado Maria Del Pilar, Fénix-Caballero Silvia, Alegre-Del Rey Emilio Jesús, de la Lastra-Romero Catalina Alarcón, Sánchez-Hidalgo Marina
Pharmacy Department, 16875Hospital Universitario Puerto Real, Cadiz, Spain.
Department of Pharmacology, 16778Universidad de Sevilla, Facultad de Farmacia, Sevilla, Spain.
J Oncol Pharm Pract. 2023 Jan;29(1):155-161. doi: 10.1177/10781552211062144. Epub 2021 Nov 30.
There is subgroup analysis suggesting a lack of benefit of daratumumab use in multiple myeloma (MM) and hepatic disease (HD). The objectives of this study were to conduct a systematic review and interpretation of daratumumab-based regimen efficacy in transplant-ineligible patients with untreated MM and HD.
A systematic search in Pubmed database about randomized clinical trials (RCTs) with subgroup analysis regarding hepatic function for overall survival (OS) or progression-free survival (PFS) were developed. Two methodologies were applied. One of them considered statistical interaction, prespecification, biological support and consistency of subgroup results. Second methodology was two-part validated tool: preliminary questions to reject subset analysis without minimal relevance, and a checklist relating a recommendation for applicability in clinical practice.
It was included three records. About first methodology, statistical interaction among subgroups was found for PFS in one RCT. Subsets were prespecified in all RCTs. Biological support of efficacy differences could be reasonable. Inconsistent results were found. Second methology directly rejected applicability of subset analysis in two records. Checklist recommended "null" application of results in the remaining RCT.
No consistent heterogeneity for daratumumab-based regimen efficacy was observed among subgroups regarding hepatic function in transplant-ineligible patients with untreated MM. Patients with normal hepatic function and HD could benefit from these treatments.
亚组分析表明，达雷妥尤单抗在多发性骨髓瘤（MM）和肝脏疾病（HD）中使用并无益处。本研究的目的是对未接受治疗的MM合并HD且不符合移植条件的患者，基于达雷妥尤单抗的治疗方案疗效进行系统评价和解读。
在PubMed数据库中进行系统检索，检索关于肝功能亚组分析的随机临床试验（RCT），以评估总生存期（OS）或无进展生存期（PFS）。应用了两种方法。其中一种方法考虑了统计交互作用、预先设定、生物学支持以及亚组结果的一致性。第二种方法是两部分验证工具：用于排除相关性极小的亚组分析的初步问题，以及一份与临床实践适用性建议相关的清单。
纳入了三项记录。关于第一种方法，在一项RCT中发现亚组间PFS存在统计交互作用。所有RCT中均预先设定了亚组。疗效差异的生物学支持可能是合理的。结果存在不一致性。第二种方法直接排除了两项记录中亚组分析的适用性。清单建议在其余RCT中“无效”应用结果。
在未接受治疗的MM合并HD且不符合移植条件的患者中，未观察到达雷妥尤单抗治疗方案疗效在肝功能亚组间存在一致的异质性。肝功能正常且患有HD的患者可能从这些治疗中获益。
