背景:对于复发/难治性(RR)滤泡性淋巴瘤(FL),既往治疗≥2次后,尚无既定的治疗标准。我们进行了间接治疗比较(ITC),以比较莫苏妥珠单抗与此设置中可用治疗的疗效和耐受性。
方法:进行了系统的文献综述(SLR)和随后的可行性评估,以确定在设计方面最合适的比较研究,可用的终点和种群。使用匹配调整间接比较(MAIC)和基于倾向评分的方法来解释NCT02500407和以汇总或患者水平数据可用性为特征的研究之间的患者特征不平衡。分别。
结果:ZUMA-5,ELARA,DELTA,DYNAMO,UNITY-NHL,AUGMENT和NCT01897571通过了MAIC可行性评估。患者水平的数据可从GADOLIN获得,CONTRALTO和NCT02257567。MAIC结果在EHZ2野生型患者中,对于所有结果,莫苏妥珠单抗均优于他泽美司他,对于完全反应(CR),PI3K抑制剂均优于他泽司他。客观反应率(ORR),因不良事件和无进展生存期(PFS)而停药。MAIC青睐CART治疗PFS和,在较小程度上,ORR和CR。与基于抗CD20抗体的方案的比较产生混合结果。
结论:ITC表明,mosumetuzumab可能导致优于tazemetostat(在EHZ2野生型患者中)和PI3K抑制剂的结果,并且可能是一个有希望的替代方案,可以在≥2种抗CD20系列后复发的患者中使用不同的抗CD20方案进行重新挑战。虽然初步结果有点有利于CART疗法,由于研究设计的内在差异,局限性和不确定性仍然存在。因此,对于≥2次既往治疗后的RRFL患者,Mosumetuzumab可能是一种有希望的治疗选择。
No established standard of care exists for relapsed/refractory (RR) follicular lymphoma (FL) after ≥2 prior therapies. We conducted indirect treatment comparisons (ITCs) to compare the efficacy and tolerability of mosunetuzumab with those of available treatments used in this setting.
A systematic literature review (SLR) and subsequent feasibility assessments were conducted to identify the most suitable comparator studies in terms of design, available endpoints and populations. Imbalances in patient characteristics between NCT02500407 and studies featuring aggregate or patient-level data availability were accounted for using matching-adjusted indirect comparison (MAIC) and propensity score-based methodologies, respectively.
ZUMA-5, ELARA, DELTA, DYNAMO, UNITY-NHL, AUGMENT and NCT01897571 passed the MAIC feasibility assessment. Patient-level data were available from GADOLIN, CONTRALTO and NCT02257567. MAIC results generally favored mosunetuzumab over tazemetostat in EHZ2wild-type patients for all outcomes and over PI3K inhibitors for complete response (CR), objective response rate (ORR), discontinuations due to adverse events and progression-free survival (PFS) with umbralisib. MAICs favored CART therapies for PFS and, to a lesser extent, ORR and CR. Comparisons with anti-CD20 antibody-based regimens yielded mixed results.
ITCs suggest that mosunetuzumab may lead to superior outcomes over tazemetostat (in EHZ2wild-type patients) and PI3K inhibitors and may be a promising alternative to re-challenging with a different anti-CD20 regimen in patients who relapse after ≥2 prior anti-CD20 lines. Although preliminary results somewhat favored CART therapies, limitations and uncertainties remain because of intrinsic differences in study design. Mosunetuzumab could thus be a promising treatment option for patients with RR FL after ≥2 prior therapies.