{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T23:18:52Z","timestamp":1782429532216,"version":"3.54.5"},"reference-count":35,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2021,11,29]],"date-time":"2021-11-29T00:00:00Z","timestamp":1638144000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Ciltacabtagene autoleucel (cilta-cel) is a Chimeric antigen receptor T-cell therapy with the potential for long-term disease control in heavily pre-treated patients with relapsed\/refractory multiple myeloma (RRMM). As cilta-cel was assessed in the single-arm CARTITUDE-1 clinical trial, we used an external cohort of patients from the Therapie Monitor registry fulfilling the CARTITUDE-1 inclusion criteria to evaluate the effectiveness of cilta-cel for overall survival (OS) and time to next treatment (TTNT) vs. real-world clinical practice. Individual patient data allowed us to adjust the comparisons between both cohorts, using the inverse probability of treatment weighting (IPW; average treatment effect in the treated population (ATT) and overlap population (ATO) weights) and multivariable Cox proportional hazards regression. Outcomes were compared in intention-to-treat (HR, IPW-ATT: TTNT: 0.13 (95% CI: 0.07, 0.24); OS: 0.14 (95% CI: 0.07, 0.25); IPW-ATO: TTNT: 0.24 (95% CI: 0.12, 0.49); OS: 0.26 (95% CI: 0.13, 0.54)) and modified intention-to-treat (HR, IPW-ATT: TTNT: 0.24 (95% CI: 0.09, 0.67); OS: 0.26 (95% CI: 0.08, 0.84); IPW-ATO: TTNT: 0.26 (95% CI: 0.11, 0.59); OS: 0.31 (95% CI: 0.12, 0.79)) populations. All the comparisons were statistically significant in favor of cilta-cel. These results highlight cilta-cel\u2019s potential as a novel, effective treatment to address unmet needs in patients with RRMM.<\/jats:p>","DOI":"10.3390\/cancers13235996","type":"journal-article","created":{"date-parts":[[2021,11,29]],"date-time":"2021-11-29T22:50:45Z","timestamp":1638226245000},"page":"5996","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Adjusted Comparison of Outcomes between Patients from CARTITUDE-1 versus Multiple Myeloma Patients with Prior Exposure to PI, Imid and Anti-CD-38 from a German Registry"],"prefix":"10.3390","volume":"13","author":[{"given":"Maximilian","family":"Merz","sequence":"first","affiliation":[{"name":"Cell Therapy and Hemostaseology, Department of Hematology, University Hospital of Leipzig, 04103 Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0961-0035","authenticated-orcid":false,"given":"Hartmut","family":"Goldschmidt","sequence":"additional","affiliation":[{"name":"Internal Medicine V and National Center for Tumor Diseases, University Clinic Heidelberg, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Parameswaran","family":"Hari","sequence":"additional","affiliation":[{"name":"Medical College of Wisconsin, Milwaukee, WI 53226, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mounzer","family":"Agha","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9456-9120","authenticated-orcid":false,"given":"Joris","family":"Diels","sequence":"additional","affiliation":[{"name":"Janssen Pharmaceutica NV, 2340 Beerse, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Ghilotti","sequence":"additional","affiliation":[{"name":"Janssen-Cilag SpA, 20093 Cologno Monzese, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nolen J.","family":"Perualila","sequence":"additional","affiliation":[{"name":"Janssen Pharmaceutica NV, 2340 Beerse, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jedelyn","family":"Cabrieto","sequence":"additional","affiliation":[{"name":"Janssen Pharmaceutica NV, 2340 Beerse, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7802-0883","authenticated-orcid":false,"given":"Benjamin","family":"Haefliger","sequence":"additional","affiliation":[{"name":"Cilag GmbH International, 6300 Zug, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik","family":"Sliwka","sequence":"additional","affiliation":[{"name":"Janssen-Cilag Pharma GmbH, 1020 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordan M.","family":"Schecter","sequence":"additional","affiliation":[{"name":"Janssen R&D, Raritan, NJ 08869, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolyn C.","family":"Jackson","sequence":"additional","affiliation":[{"name":"Janssen R&D, Raritan, NJ 08869, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunsi","family":"Olyslager","sequence":"additional","affiliation":[{"name":"Janssen Pharmaceutica NV, 2340 Beerse, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad","family":"Akram","sequence":"additional","affiliation":[{"name":"Legend Biotech USA, Inc., Piscataway, NJ 08854, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tonia","family":"Nesheiwat","sequence":"additional","affiliation":[{"name":"Legend Biotech USA, Inc., Piscataway, NJ 08854, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lenka","family":"Kellermann","sequence":"additional","affiliation":[{"name":"Oncology Information Service (O.I.S), 79098 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sundar","family":"Jagannath","sequence":"additional","affiliation":[{"name":"Mount Sinai Medical Center, New York, NY 10029, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1038\/leu.2008.291","article-title":"Criteria for diagnosis, staging, risk stratification and response assessment of multiple myeloma","volume":"23","author":"Kyle","year":"2009","journal-title":"Leukemia"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1111\/bjh.14193","article-title":"Multiple myeloma: Practice patterns across Europe","volume":"175","author":"Raab","year":"2016","journal-title":"Br. J. Haematol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"3259","DOI":"10.1182\/blood-2018-99-115985","article-title":"Real-Life Data on the Outcome of Daratumomab-Refractory Myeloma Patients: Multi-Center Experience","volume":"132","author":"Benyamini","year":"2018","journal-title":"Blood"},{"key":"ref_4","unstructured":"Haefliger, B., Diels, J., Ghilotti, F., Sliwka, H., Potamianou, A., Bacon, T., and Kellermann, L. (2021, January 9\u201317). Baseline characteristics and survival outcomes of patients with tri exposed multiple myeloma in a German registry. Proceedings of the EHA2021\u2014European Hematology Association Conference, Virtual Meeting."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1374","DOI":"10.1016\/j.ejca.2012.12.027","article-title":"Cancer incidence and mortality patterns in Europe: Estimates for 40 countries in 2012","volume":"49","author":"Ferlay","year":"2013","journal-title":"Eur. J. Cancer Oxf. Engl."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e447","DOI":"10.1016\/S2352-3026(20)30081-8","article-title":"Daratumumab monotherapy in patients with heavily pretreated relapsed or refractory multiple myeloma: Final resultsfrom the phase 2 GEN501 and SIRIUS trials","volume":"7","author":"Usmani","year":"2020","journal-title":"Lancet Haematol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1016\/S1470-2045(13)70380-2","article-title":"Pomalidomide plus low-dose dexamethasone versus high-dose dexamethasone alone for patients with relapsed and refractory multiple myeloma (MM-003): A randomised, open-label, phase 3 trial","volume":"14","author":"Miguel","year":"2013","journal-title":"Lancet Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1016\/S1470-2045(14)70440-1","article-title":"Panobinostat plus bortezomib and dexamethasone versus placebo plus bortezomib and dexamethasone in patients with relapsed or relapsed and refractory multiple myeloma: A multicentre, randomised, double-blind phase 3 trial","volume":"15","author":"Hungria","year":"2014","journal-title":"Lancet Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3892","DOI":"10.1200\/JCO.2006.10.5460","article-title":"Randomized phase III study of pegylated liposomal doxorubicin plus bortezomib compared with bortezomib alone in relapsed or refractory multiple myeloma: Combination therapy improves time to progression","volume":"25","author":"Orlowski","year":"2007","journal-title":"J. Clin. Oncol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/S1470-2045(15)00464-7","article-title":"Carfilzomib and dexamethasone versus bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma (ENDEAVOR): A randomised, phase 3, open-label, multicentre study","volume":"17","author":"Dimopoulos","year":"2016","journal-title":"Lancet Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2147","DOI":"10.1038\/leu.2009.147","article-title":"Long-term follow-up on overall survival from the MM-009 and MM-010 phase III trials of lenalidomide plus dexamethasone in patients with relapsed or refractory multiple myeloma","volume":"23","author":"Dimopoulos","year":"2009","journal-title":"Leukemia"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.annonc.2020.11.014","article-title":"Multiple myeloma: EHA-ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up","volume":"32","author":"Dimopoulos","year":"2021","journal-title":"Ann. Oncol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2266","DOI":"10.1038\/s41375-019-0435-7","article-title":"Outcomes of patients with multiple myeloma refractory to CD38-targeted monoclonal antibody therapy","volume":"33","author":"Gandhi","year":"2019","journal-title":"Leukemia"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/j.ctrv.2018.09.001","article-title":"Drug resistance in multiple myeloma","volume":"70","author":"Robak","year":"2018","journal-title":"Cancer Treat. Rev."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e449","DOI":"10.1016\/j.clml.2020.12.023","article-title":"Trends in Early Mortality from Multiple Myeloma: A Population-Based Analysis","volume":"21","author":"Kumar","year":"2021","journal-title":"Clin. Lymphoma Myeloma Leuk."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1038\/s41591-019-0564-6","article-title":"Clinical lessons learned from the first leg of the CAR T cell journey","volume":"25","author":"Majzner","year":"2019","journal-title":"Nat. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1182\/blood-2020-136307","article-title":"CARTITUDE-1: Phase 1b\/2 Study of Ciltacabtagene Autoleucel, a B-Cell Maturation Antigen\u2013Directed Chimeric Antigen Receptor T Cell Therapy, in Relapsed\/Refractory Multiple Myeloma","volume":"136","author":"Madduri","year":"2020","journal-title":"Blood"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1016\/S0140-6736(21)00933-8","article-title":"Ciltacabtagene autoleucel, a B-cell maturation antigen-directed chimeric antigen receptor T-cell therapy in patients with relapsed or refractory multiple myeloma (CARTITUDE-1): A phase 1b\/2 open-label study","volume":"398","author":"Berdeja","year":"2021","journal-title":"Lancet"},{"key":"ref_19","unstructured":"ClinicalTrials.gov (2021, June 15). A Study of JNJ-68284528, a Chimeric Antigen Receptor T Cell (CAR-T) Therapy Directed against B-Cell Maturation Antigen (BCMA) in Participants with Relapsed or Refractory Multiple Myeloma (CARTITUDE-1), Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03548207."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Usmani, S., Berdeja, J., Madduri, D., Jakubowiak, A., Agha, M., Cohen, D., Hari, P., Yeh, T.M., Olyslager, Y., and Banerjee, A. (2021, January 4\u20138). Ciltacabtagene autoleucel, a B-cell maturation antigen (BCMA)-directed chimeric antigen receptor T-cell (CAR-T) therapy, in relapsed\/refractory multiple myeloma (R\/R MM): Updated results from CARTITUDE-1. Proceedings of the American Society of Clinical Oncology (ASCO) Annual Meeting, Virtual Meeting.","DOI":"10.1200\/JCO.2021.39.15_suppl.8005"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"4734","DOI":"10.1182\/blood-2019-128030","article-title":"Treatment Patterns in Patients (pts) with Refractory\/Relapsed Multiple Myeloma (RRMM) in Germany between 2016 and 2018","volume":"134","author":"Merz","year":"2019","journal-title":"Blood"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1002\/pst.2107","article-title":"How to choose a time zero for patients in external control arms","volume":"20","author":"Backenroth","year":"2021","journal-title":"Pharm. Stat."},{"key":"ref_23","first-page":"4","article-title":"History-adjusted marginal structural models and statically-optimal dynamic treatment regimens","volume":"1","author":"Petersen","year":"2005","journal-title":"Int. J. Biostat."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1093\/aje\/kwm232","article-title":"History-adjusted marginal structural models for estimating time-varying effect modification","volume":"166","author":"Petersen","year":"2007","journal-title":"Am. J. Epidemiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1093\/aje\/kwv254","article-title":"Using Big Data to Emulate a Target Trial When a Randomized Trial Is Not Available","volume":"183","author":"Robins","year":"2016","journal-title":"Am. J. Epidemiol."},{"key":"ref_26","unstructured":"Yang, D., and Dalton, J. (2012, January 22\u201325). A unified approach to measuring the effect size between two groups using SAS\u00ae. Proceedings of the SAS Global Forum, Orlando, FL, USA."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1080\/01621459.2016.1260466","article-title":"Balancing Covariates via Propensity Score Weighting","volume":"113","author":"Li","year":"2018","journal-title":"J. Am. Stat. Assoc."},{"key":"ref_28","first-page":"250","article-title":"Addressing Extreme Propensity Scores via the Overlap Weights","volume":"188","author":"Li","year":"2019","journal-title":"Am. J. Epidemiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1093\/biomet\/81.3.515","article-title":"Proportional hazards tests and diagnostics based on weighted residuals","volume":"81","author":"Grambsch","year":"1994","journal-title":"Biometrika"},{"key":"ref_30","unstructured":"Mehra, M., Vogel, M., Valluri, S., Nair, S., Schecter, J., Slowik, R., Jagannath, S., Weisel, K., and Usmani, S. (2020, January 11\u201321). Patient characteristics, treatment patterns and outcomes in patients with triple class refractory multiple myeloma. Proceedings of the EHA25 VIRTUAL: 25th EHA Annual Congress: \u201cUnfolding the future!\u201d, Virtual Meeting."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3115","DOI":"10.1182\/blood-2019-122706","article-title":"Evolving Treatment Trends in Relapsed\/Refractory Multiple Myeloma in Europe from 2016 to 2018: Analysis of a Multi-National Survey","volume":"134","author":"Merz","year":"2019","journal-title":"Blood"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1007\/s00277-017-2991-0","article-title":"Diagnosis and treatment of multiple myeloma in Germany: Analysis of a nationwide multi-institutional survey","volume":"96","author":"Merz","year":"2017","journal-title":"Ann. Hematol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"8030","DOI":"10.1200\/JCO.2021.39.15_suppl.8030","article-title":"Cilta-cel versus conventional treatment in patients with relapse\/refractory multiple myeloma","volume":"39","author":"Costa","year":"2021","journal-title":"J. Clin. Oncol."},{"key":"ref_34","unstructured":"Weisel, K., Martin, T., Krishnan, A., Jagannath, S., Qi, K., Londhe, A., Mehra, M., Nair, S., Diels, J., and Vogel, M. (2021, January 9\u201317). Comparison of ciltacabtagene autoleucel (cilta-cel) in CARTITUDE-1 versus standard of care in triple-class exposed multiple myeloma patients in clinical trials of daratumumab. Proceedings of the EHA2021\u2014European Hematology Association Conference, Virtual Meeting."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"8045","DOI":"10.1200\/JCO.2021.39.15_suppl.8045","article-title":"Comparison of outcomes with ciltacabtagene autoleucel (cilta-cel) in CARTITUDE-1 versus real-world standard of care (RW SOC) for patients with triple-class exposed relapsed\/refractory multiple myeloma","volume":"39","author":"Martin","year":"2021","journal-title":"J. Clin. Oncol."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/13\/23\/5996\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:37:13Z","timestamp":1760168233000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/13\/23\/5996"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,29]]},"references-count":35,"journal-issue":{"issue":"23","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["cancers13235996"],"URL":"https:\/\/doi.org\/10.3390\/cancers13235996","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,29]]}}}