Cyrille Touzeau, Brea Lipe, Abdullah M. Khan, Binod Dhakal, Sandhya Nair, Jianming He, João Mendes, Seina Lee, Carolina Lonardi, Ana Slaughter, Nikoletta Lendvai, Jordan M. Schecter, Diana Chen, Man Zhao, Tzu-min Yeh, Xavier Leleu, Noemí Puig, Dominik Dytfeld, Elena Zamagni, Katja Weisel, Lionel Karlin, Michel Delforge, Paolo Corradini, Roberto Mina, Wilfried Roeloffzen, Surbhi Sidana
{"title":"来那度胺难治性多发性骨髓瘤在cartitde -4中，西他他烯自甲醇与来自Flatiron注册的现实世界医生选择的治疗方法的有效性比较。","authors":"Cyrille Touzeau, Brea Lipe, Abdullah M. Khan, Binod Dhakal, Sandhya Nair, Jianming He, João Mendes, Seina Lee, Carolina Lonardi, Ana Slaughter, Nikoletta Lendvai, Jordan M. Schecter, Diana Chen, Man Zhao, Tzu-min Yeh, Xavier Leleu, Noemí Puig, Dominik Dytfeld, Elena Zamagni, Katja Weisel, Lionel Karlin, Michel Delforge, Paolo Corradini, Roberto Mina, Wilfried Roeloffzen, Surbhi Sidana","doi":"10.1007/s12325-025-03308-2","DOIUrl":null,"url":null,"abstract":"<div><h3>Introduction</h3><p>Ciltacabtagene autoleucel (cilta-cel) is approved for relapsed or refractory multiple myeloma (RRMM). In the CARTITUDE-4 study (NCT04181827), cilta-cel demonstrated superior efficacy versus pomalidomide, bortezomib, and dexamethasone or daratumumab, pomalidomide, and dexamethasone in patients with RRMM after 1–3 prior lines of therapy (LOT). We conducted an indirect treatment comparison to understand the comparative efficacy of cilta-cel versus real-world (RW) physician’s choice of treatment for lenalidomide-refractory MM.</p><h3>Methods</h3><p>De-identified data from the Flatiron Health MM cohort registry (January 2020 to May 2024) were compared with data from CARTITUDE-4 (data cutoff May 1, 2024). Key eligibility criteria for CARTITUDE-4 were used to match patients from the Flatiron database. Baseline covariates of prognostic significance were adjusted using inverse probability of treatment weighting. Outcomes for comparative effectiveness included progression-free survival (PFS), RW PFS, time to next treatment (TTNT), and overall survival (OS). Sensitivity analyses were conducted.</p><h3>Results</h3><p>The CARTITUDE-4 cohort included data from 208 patients who received cilta-cel; the median follow-up was 33.6 months. The real-world cohort included 932 patients (1445 eligible LOT) from the Flatiron database; the median follow-up was 23.6 months. In base case analyses, compared with the Flatiron cohort, patients treated with cilta-cel had improved PFS (hazard ratio [HR] 0.29 [95% confidence interval (CI)] 0.22–0.36; <i>p</i> < 0.001), RW-PFS (HR 0.29 [95% CI 0.23–0.37]; <i>p</i> < 0.001), TTNT (HR 0.32 [95% CI 0.25–0.41]; <i>p</i> < 0.001), and OS (HR 0.59 [95% CI 0.41–0.84]; <i>p</i> = 0.003). These findings were consistent across all sensitivity analyses.</p><h3>Conclusion</h3><p>Cilta-cel lengthened TTNT and demonstrated meaningful prolongation in PFS and OS compared with real-world physician’s choice for lenalidomide-refractory MM. These data highlight the value of cilta-cel as an effective therapy in earlier-line patients with relapsed, lenalidomide-refractory MM exposed to proteasome inhibitors and immunomodulatory drugs.</p><h3>Trial registration</h3><p>CARTITUDE-4: ClinicalTrials.gov ID NCT04181827.</p></div>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":"42 10","pages":"5023 - 5041"},"PeriodicalIF":4.0000,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12325-025-03308-2.pdf","citationCount":"0","resultStr":"{\"title\":\"Comparative Effectiveness of Ciltacabtagene Autoleucel in CARTITUDE-4 Versus Real-World Physician’s Choice of Therapy from the Flatiron Registry in Lenalidomide-Refractory Multiple Myeloma\",\"authors\":\"Cyrille Touzeau, Brea Lipe, Abdullah M. Khan, Binod Dhakal, Sandhya Nair, Jianming He, João Mendes, Seina Lee, Carolina Lonardi, Ana Slaughter, Nikoletta Lendvai, Jordan M. Schecter, Diana Chen, Man Zhao, Tzu-min Yeh, Xavier Leleu, Noemí Puig, Dominik Dytfeld, Elena Zamagni, Katja Weisel, Lionel Karlin, Michel Delforge, Paolo Corradini, Roberto Mina, Wilfried Roeloffzen, Surbhi Sidana\",\"doi\":\"10.1007/s12325-025-03308-2\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Introduction</h3><p>Ciltacabtagene autoleucel (cilta-cel) is approved for relapsed or refractory multiple myeloma (RRMM). In the CARTITUDE-4 study (NCT04181827), cilta-cel demonstrated superior efficacy versus pomalidomide, bortezomib, and dexamethasone or daratumumab, pomalidomide, and dexamethasone in patients with RRMM after 1–3 prior lines of therapy (LOT). We conducted an indirect treatment comparison to understand the comparative efficacy of cilta-cel versus real-world (RW) physician’s choice of treatment for lenalidomide-refractory MM.</p><h3>Methods</h3><p>De-identified data from the Flatiron Health MM cohort registry (January 2020 to May 2024) were compared with data from CARTITUDE-4 (data cutoff May 1, 2024). Key eligibility criteria for CARTITUDE-4 were used to match patients from the Flatiron database. Baseline covariates of prognostic significance were adjusted using inverse probability of treatment weighting. Outcomes for comparative effectiveness included progression-free survival (PFS), RW PFS, time to next treatment (TTNT), and overall survival (OS). Sensitivity analyses were conducted.</p><h3>Results</h3><p>The CARTITUDE-4 cohort included data from 208 patients who received cilta-cel; the median follow-up was 33.6 months. The real-world cohort included 932 patients (1445 eligible LOT) from the Flatiron database; the median follow-up was 23.6 months. In base case analyses, compared with the Flatiron cohort, patients treated with cilta-cel had improved PFS (hazard ratio [HR] 0.29 [95% confidence interval (CI)] 0.22–0.36; <i>p</i> < 0.001), RW-PFS (HR 0.29 [95% CI 0.23–0.37]; <i>p</i> < 0.001), TTNT (HR 0.32 [95% CI 0.25–0.41]; <i>p</i> < 0.001), and OS (HR 0.59 [95% CI 0.41–0.84]; <i>p</i> = 0.003). These findings were consistent across all sensitivity analyses.</p><h3>Conclusion</h3><p>Cilta-cel lengthened TTNT and demonstrated meaningful prolongation in PFS and OS compared with real-world physician’s choice for lenalidomide-refractory MM. These data highlight the value of cilta-cel as an effective therapy in earlier-line patients with relapsed, lenalidomide-refractory MM exposed to proteasome inhibitors and immunomodulatory drugs.</p><h3>Trial registration</h3><p>CARTITUDE-4: ClinicalTrials.gov ID NCT04181827.</p></div>\",\"PeriodicalId\":7482,\"journal\":{\"name\":\"Advances in Therapy\",\"volume\":\"42 10\",\"pages\":\"5023 - 5041\"},\"PeriodicalIF\":4.0000,\"publicationDate\":\"2025-08-06\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://link.springer.com/content/pdf/10.1007/s12325-025-03308-2.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Advances in Therapy\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://link.springer.com/article/10.1007/s12325-025-03308-2\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"MEDICINE, RESEARCH & EXPERIMENTAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Advances in Therapy","FirstCategoryId":"3","ListUrlMain":"https://link.springer.com/article/10.1007/s12325-025-03308-2","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
Comparative Effectiveness of Ciltacabtagene Autoleucel in CARTITUDE-4 Versus Real-World Physician’s Choice of Therapy from the Flatiron Registry in Lenalidomide-Refractory Multiple Myeloma
Introduction
Ciltacabtagene autoleucel (cilta-cel) is approved for relapsed or refractory multiple myeloma (RRMM). In the CARTITUDE-4 study (NCT04181827), cilta-cel demonstrated superior efficacy versus pomalidomide, bortezomib, and dexamethasone or daratumumab, pomalidomide, and dexamethasone in patients with RRMM after 1–3 prior lines of therapy (LOT). We conducted an indirect treatment comparison to understand the comparative efficacy of cilta-cel versus real-world (RW) physician’s choice of treatment for lenalidomide-refractory MM.
Methods
De-identified data from the Flatiron Health MM cohort registry (January 2020 to May 2024) were compared with data from CARTITUDE-4 (data cutoff May 1, 2024). Key eligibility criteria for CARTITUDE-4 were used to match patients from the Flatiron database. Baseline covariates of prognostic significance were adjusted using inverse probability of treatment weighting. Outcomes for comparative effectiveness included progression-free survival (PFS), RW PFS, time to next treatment (TTNT), and overall survival (OS). Sensitivity analyses were conducted.
Results
The CARTITUDE-4 cohort included data from 208 patients who received cilta-cel; the median follow-up was 33.6 months. The real-world cohort included 932 patients (1445 eligible LOT) from the Flatiron database; the median follow-up was 23.6 months. In base case analyses, compared with the Flatiron cohort, patients treated with cilta-cel had improved PFS (hazard ratio [HR] 0.29 [95% confidence interval (CI)] 0.22–0.36; p < 0.001), RW-PFS (HR 0.29 [95% CI 0.23–0.37]; p < 0.001), TTNT (HR 0.32 [95% CI 0.25–0.41]; p < 0.001), and OS (HR 0.59 [95% CI 0.41–0.84]; p = 0.003). These findings were consistent across all sensitivity analyses.
Conclusion
Cilta-cel lengthened TTNT and demonstrated meaningful prolongation in PFS and OS compared with real-world physician’s choice for lenalidomide-refractory MM. These data highlight the value of cilta-cel as an effective therapy in earlier-line patients with relapsed, lenalidomide-refractory MM exposed to proteasome inhibitors and immunomodulatory drugs.
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.
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