Survival Outcomes with Cilta-cel Versus Conventional Treatment Regimens for Patients with Lenalidomide-Refractory Multiple Myeloma Using Inverse Probability of Treatment Weighting.
Rafael Fonseca, Joris Diels, Francesca Ghilotti, João Mendes, Sandra Van Hoorenbeeck, Seina Lee, Jordan M Schecter, Nikoletta Lendvai, Nitin Patel, Ana Triguero, Winfried Alsdorf, Niels W C J van de Donk, Margherita Ursi
{"title":"Survival Outcomes with Cilta-cel Versus Conventional Treatment Regimens for Patients with Lenalidomide-Refractory Multiple Myeloma Using Inverse Probability of Treatment Weighting.","authors":"Rafael Fonseca, Joris Diels, Francesca Ghilotti, João Mendes, Sandra Van Hoorenbeeck, Seina Lee, Jordan M Schecter, Nikoletta Lendvai, Nitin Patel, Ana Triguero, Winfried Alsdorf, Niels W C J van de Donk, Margherita Ursi","doi":"10.1007/s12325-025-03278-5","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>The phase 3 CARTITUDE-4 trial demonstrated superiority of ciltacabtagene autoleucel (cilta-cel) over daratumumab, pomalidomide and dexamethasone, or pomalidomide, bortezomib and dexamethasone, in lenalidomide-refractory patients with relapsed/refractory multiple myeloma (RRMM) who received 1-3 prior lines of therapy. The comparative efficacy of cilta-cel was previously evaluated against other common regimens. Here, we present an updated comparative efficacy assessment, including OS, between cilta-cel (CARTITUDE-4 34-month median follow-up) and common regimens.</p><p><strong>Methods: </strong>Individual patient data were available from CARTITUDE-4 (cilta-cel), CASTOR (daratumumab, bortezomib and dexamethasone [DVd]), CANDOR (daratumumab, carfilzomib and dexamethasone [DKd] and carfilzomib and dexamethasone [Kd]) and APOLLO (pomalidomide and dexamethasone [Pd]). Inverse probability of treatment weighting (IPTW) was used to adjust for key baseline patient characteristic imbalances. Relative efficacies were estimated with response rate ratios and 95% confidence intervals (CIs) for response rates, with hazard ratios (HRs) and 95% CIs for PFS and OS. Sensitivity analyses using alternative statistical approaches were explored.</p><p><strong>Results: </strong>After excluding 53 patients with prior anti-CD38 therapy exposure, cilta-cel (n = 155) was compared with DVd (n = 44), DKd (n = 98), Kd (n = 46) and Pd (n = 92). Baseline covariates were generally well balanced across cohorts after IPTW. Cilta-cel showed significant improvements in PFS (HR 0.21-0.58; p ≤ 0.01) and OS (HR 0.31-0.55; p < 0.05) vs all regimens. With longer follow-up, the relative benefit of cilta-cel versus other regimens further increased on deeper levels of response. Although all results, except ORR, significantly favored cilta-cel, the DKd comparison provided the most conservative estimates.</p><p><strong>Conclusion: </strong>This updated analysis confirms previously observed significant superiority of PFS and response outcomes of cilta-cel while showing significant OS benefit compared with common regimens for this population. These findings support cilta-cel as an effective treatment for lenalidomide-refractory RRMM patients as early as second line.</p><p><strong>Trial registration: </strong>CARTITUDE-4 ClinicalTrials.gov ID: NCT04181827.</p>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":" ","pages":""},"PeriodicalIF":3.4000,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Advances in Therapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s12325-025-03278-5","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
引用次数: 0
Abstract
Introduction: The phase 3 CARTITUDE-4 trial demonstrated superiority of ciltacabtagene autoleucel (cilta-cel) over daratumumab, pomalidomide and dexamethasone, or pomalidomide, bortezomib and dexamethasone, in lenalidomide-refractory patients with relapsed/refractory multiple myeloma (RRMM) who received 1-3 prior lines of therapy. The comparative efficacy of cilta-cel was previously evaluated against other common regimens. Here, we present an updated comparative efficacy assessment, including OS, between cilta-cel (CARTITUDE-4 34-month median follow-up) and common regimens.
Methods: Individual patient data were available from CARTITUDE-4 (cilta-cel), CASTOR (daratumumab, bortezomib and dexamethasone [DVd]), CANDOR (daratumumab, carfilzomib and dexamethasone [DKd] and carfilzomib and dexamethasone [Kd]) and APOLLO (pomalidomide and dexamethasone [Pd]). Inverse probability of treatment weighting (IPTW) was used to adjust for key baseline patient characteristic imbalances. Relative efficacies were estimated with response rate ratios and 95% confidence intervals (CIs) for response rates, with hazard ratios (HRs) and 95% CIs for PFS and OS. Sensitivity analyses using alternative statistical approaches were explored.
Results: After excluding 53 patients with prior anti-CD38 therapy exposure, cilta-cel (n = 155) was compared with DVd (n = 44), DKd (n = 98), Kd (n = 46) and Pd (n = 92). Baseline covariates were generally well balanced across cohorts after IPTW. Cilta-cel showed significant improvements in PFS (HR 0.21-0.58; p ≤ 0.01) and OS (HR 0.31-0.55; p < 0.05) vs all regimens. With longer follow-up, the relative benefit of cilta-cel versus other regimens further increased on deeper levels of response. Although all results, except ORR, significantly favored cilta-cel, the DKd comparison provided the most conservative estimates.
Conclusion: This updated analysis confirms previously observed significant superiority of PFS and response outcomes of cilta-cel while showing significant OS benefit compared with common regimens for this population. These findings support cilta-cel as an effective treatment for lenalidomide-refractory RRMM patients as early as second line.
期刊介绍：
Advances in Therapy is an international, peer reviewed, rapid-publication (peer review in 2 weeks, published 3–4 weeks from acceptance) journal dedicated to the publication of high-quality clinical (all phases), observational, real-world, and health outcomes research around the discovery, development, and use of therapeutics and interventions (including devices) across all therapeutic areas. Studies relating to diagnostics and diagnosis, pharmacoeconomics, public health, epidemiology, quality of life, and patient care, management, and education are also encouraged.
The journal is of interest to a broad audience of healthcare professionals and publishes original research, reviews, communications and letters. The journal is read by a global audience and receives submissions from all over the world. Advances in Therapy will consider all scientifically sound research be it positive, confirmatory or negative data. Submissions are welcomed whether they relate to an international and/or a country-specific audience, something that is crucially important when researchers are trying to target more specific patient populations. This inclusive approach allows the journal to assist in the dissemination of all scientifically and ethically sound research.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
