Supplementary materials: Efficacy of CARVYKTI in CARTITUDE-4 versus other conventional treatment regimens for lenalidomide-refractory multiple myeloma using inverse probability of treatment weighting

These are peer-reviewed supplementary materials for the article 'Efficacy of CARVYKTI in CARTITUDE-4 versus other conventional treatment regimens for lenalidomide-refractory multiple myeloma using inverse probability of treatment weighting' published in the Journal of Comparative Effectiveness Research.Table S1: Study characteristics of daratumumab clinical trialsTable S2: Availability of prognostic factors in the daratumumab clinical trialsTable S3: Multiple imputation of missing variables in CANDORTable S4: Overview of baseline characteristics for cilta-cel (CARTITUDE-4) versus DVd (CASTOR) before and after adjustment with IPTW using ATT and ATCTable S5: Overview of baseline characteristics for cilta-cel (CARTITUDE-4) versus Vd (CASTOR) before and after adjustment with IPTW using ATT and ATCTable S6: Overview of baseline characteristics for cilta-cel (CARTITUDE-4) versus DKd (CANDOR) before and after adjustment with IPTW using ATT and ATCTable S7: Overview of baseline characteristics for cilta-cel (CARTITUDE-4) versus Kd (CANDOR) before and after adjustment with IPTW using ATT and ATCTable S8: Overview of baseline characteristics for cilta-cel (CARTITUDE-4) versus Pd (APOLLO) before and after adjustment with IPTW using ATT and ATCTable S9: ATT-adjusted HR with corresponding 95% CIs using categorization of ≥3 months as the time-dependent covariate in a Cox regression modelFigure S1: RMST differences for cilta-cel versus comparatorsFigure S2: Comparative efficacy of cilta-cel versus comparators across sensitivity analyses for ORRFigure S3: Comparative efficacy of cilta-cel versus comparators across sensitivity analyses for ≥VGPRFigure S4: Comparative efficacy of cilta-cel versus comparators across sensitivity analyses for ≥CRFigure S5: Comparative efficacy of cilta-cel versus comparators across sensitivity analyses for PFSReferencesAim: The phase III randomized controlled trial (RCT) CARTITUDE-4 (NCT04181827) demonstrated superiority of CARVYKTI (ciltacabtagene autoleucel; cilta-cel) over daratumumab, pomalidomide and dexamethasone (DPd) and pomalidomide, bortezomib and dexamethasone (PVd) for relapsed/refractory multiple myeloma (RRMM) patients who have received one to three prior line(s) of therapy (LOT[s]) including an immunomodulatory agent and a proteasome inhibitor, and are refractory to lenalidomide. These analyses estimate the relative efficacy between cilta-cel and other common treatment regimens, for which no direct comparative evidence is available. Materials & methods: Patient data were available from the CARTITUDE-4, CASTOR, CANDOR and APOLLO RCTs. Imbalances between cohorts on key patient characteristics were adjusted for using inverse probability of treatment weighting (IPTW). Relative efficacies were estimated with response rate ratios (RRs) and 95% confidence intervals (CIs) for overall response rate (ORR), very good partial response or better rate (≥VGPR) and complete response or better rate (≥CR), and with hazard ratios (HRs) and 95% CIs for progression-free survival (PFS). Sensitivity analyses using different analytical methods and additional covariates were explored. Results: Key characteristics were well balanced across cohorts after IPTW. Cilta-cel showed statistically significant benefit in PFS (HRs: 0.11–0.51), ≥VGPR (RRs: 1.51–5.13) and ≥CR (RRs: 2.90–35.24) versus all comparators, and statistically significant improvements in ORR over most comparator regimens (RRs: 1.22–1.90). Results were consistent across sensitivity analyses. Conclusion: Cilta-cel demonstrated benefit over other common treatment regimens, highlighting its potential to become a new standard of care option for lenalidomide-refractory RRMM patients with one to three prior LOT(s). These comparisons help to demonstrate the improved efficacy of cilta-cel in countries where the standard of care may differ from DPd/PVd.

本数据集为发表于《比较疗效研究杂志》上的文章《CARVYKTI在CARTITUDE-4临床试验中对比其他常规治疗方案治疗来那度胺难治性多发性骨髓瘤的有效性》的同行评审补充材料。表S1：达雷木单抗临床试验研究特征；表S2：达雷木单抗临床试验中预后因素的可用性；表S3：CANDOR试验中缺失变量的多重插补；表S4：在逆概率治疗权重（IPTW）调整前后，基于ATT和ATCT的基线特征概述，比较cilta-cel（CARTITUDE-4）与DVd（CASTOR）；表S5：在逆概率治疗权重（IPTW）调整前后，基于ATT和ATCT的基线特征概述，比较cilta-cel（CARTITUDE-4）与Vd（CASTOR）；表S6：在逆概率治疗权重（IPTW）调整前后，基于ATT和ATCT的基线特征概述，比较cilta-cel（CARTITUDE-4）与DKd（CANDOR）；表S7：在逆概率治疗权重（IPTW）调整前后，基于ATT和ATCT的基线特征概述，比较cilta-cel（CARTITUDE-4）与Kd（CANDOR）；表S8：在逆概率治疗权重（IPTW）调整前后，基于ATT和ATCT的基线特征概述，比较cilta-cel（CARTITUDE-4）与Pd（APOLLO）；表S9：使用Cox回归模型中将≥3个月作为时间依赖性协变量的分类，ATT调整后的HR及其相应的95%置信区间。图S1：cilta-cel与对照药物的RMST差异；图S2：在针对ORRF进行的敏感性分析中，cilta-cel与对照药物的疗效比较；图S3：在针对≥VGPR进行的敏感性分析中，cilta-cel与对照药物的疗效比较；图S4：在针对≥CR进行的敏感性分析中，cilta-cel与对照药物的疗效比较；图S5：在针对PFS进行的敏感性分析中，cilta-cel与对照药物的疗效比较。参考文献。研究目标：CARTITUDE-4（NCT04181827）三期随机对照试验（RCT）展示了CARVYKTI（ciltacabtagene autoleucel；cilta-cel）相较于达尔西单抗、泊马度胺和地塞米松（DPd）以及泊马度胺、硼替佐米和地塞米松（PVd）在治疗接受过一线至三线治疗（LOT[s]）包括免疫调节剂和蛋白酶体抑制剂且对来那度胺难治的复发性/难治性多发性骨髓瘤（RRMM）患者中的优越性。这些分析估计了cilta-cel与其他常见治疗方案之间的相对有效性，而对于这些治疗方案，尚无直接比较的证据。材料与方法：患者数据来自CARTITUDE-4、CASTOR、CANDOR和APOLLO RCTs。使用逆概率治疗权重（IPTW）对关键患者特征队列之间的不平衡进行调整。使用总缓解率（ORR）、非常好的部分缓解或更好的比率（≥VGPR）和完全缓解或更好的比率（≥CR）的响应率比（RRs）和95%置信区间（CIs）以及无进展生存期（PFS）的HRs和95%置信区间来估计相对有效性。探讨了使用不同分析方法和额外协变量的敏感性分析。结果：在IPTW调整后，队列之间的关键特征得到了良好的平衡。cilta-cel在PFS（HRs：0.11–0.51）、≥VGPR（RRs：1.51–5.13）和≥CR（RRs：2.90–35.24）方面与所有对照药物相比显示出统计学上显著的益处，并且总缓解率（ORR）在大多数对照方案中有所显著提高（RRs：1.22–1.90）。结果在敏感性分析中保持一致。结论：cilta-cel在与其他常见治疗方案的比较中显示出益处，凸显了其成为对来那度胺难治性RRMM患者一线至三线治疗（LOT[s]）新标准治疗选择的潜力。这些比较有助于展示cilta-cel在不同国家中的改进疗效，这些国家的标准治疗可能不同于DPd/PVd。