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Published on: February 17, 2022
Cilta-cel or Standard Care in Lenalidomide-Refractory Multiple Myeloma
Jesús San-Miguel1, Binod Dhakal1, Kwee Yong1
1From the Cancer Center Clínica Universidad de Navarra, Centro Investigación Medica Aplicada, Instituto de Investigación de Navarra, Centro Investigación Biomédica en Red Cáncer (CIBERONC), Pamplona (J.S.-M.), the University Hospital of Salamanca, Instituto de Investigación Biomédica de Salamanca, Centro Investigación del Cáncer, CIBERONC, Salamanca (M.-V.M.), the Amyloidosis and Myeloma Unit, Department of Hematology, Hospital Clínic of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona (C.F.L.), the Hematological Malignancies Clinical Research Unit, Hospital 12 de Octubre Universidad Complutense, Centro Nacional de Investigaciones Oncológicas, CIBERONC, Madrid (J.M.-L.), and the Institut Català d'Oncologia and Institut Josep Carreras, Hospital Germans Trias i Pujol, Badalona (A.O.) - all in Spain; the Medical College of Wisconsin, Milwaukee (B.D.); the University College London Cancer Institute (K.Y.) and University College London Hospitals, NHS Foundation Trust (R.P.), London, University Hospitals Bristol and Weston NHS Foundation Trust, Bristol (J. Griffin), and Janssen Research and Development, High Wycombe (J. Gilbert) - all in the United Kingdom; Monash University (A. Spencer) and the Peter MacCallum Cancer Centre and Royal Melbourne Hospital, Sir Peter MacCallum Department of Oncology, University of Melbourne (S.J.H.), Melbourne, VIC, and Royal Prince Alfred Hospital and the University of Sydney, Sydney (P.J.H.) - all in Australia; the Vaccine and Infectious Disease Institute, University of Antwerp, Antwerp, and the Division of Hematology and Center for Cell Therapy and Regenerative Medicine, Antwerp University Hospital, Edegem - both in Belgium (S.A.); the Department of Hematology, University Hospital Hôtel-Dieu, Nantes (P.M., C.T.), and Service d'Hématologie et Thérapie Cellulaire, Hôpital La Milétrie, and Centre d'investigation Clinique INSERM 1402, Poitiers University Hospital, Poitiers (X.L.) - both in France; Tel Aviv Sourasky Medical Center (I.A., Y.C.C.) and the Sackler Faculty of Medicine, Tel Aviv University (Y.C.C.) - both in Tel Aviv, Israel; IRCCS Azienda Ospedaliero-Universitaria di Bologna, Seràgnoli Institute of Hematology, and the Department of Medical and Surgical Sciences, Bologna University School of Medicine, Bologna, Italy (M.C.); the Department of Hematology, Japanese Red Cross Medical Center, Tokyo (T.I.); the Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea (S.J.K.); the Department of Hematology, University Medical Center Groningen, Groningen (W.R.), and Amsterdam University Medical Center, Vrije Universiteit Amsterdam, Amsterdam (N.W.C.J.D.) - both in the Netherlands; Poznan University of Medical Sciences, Poznan, Poland (D.D.); Stanford University School of Medicine, Stanford, CA (S.S.); the University of Alabama at Birmingham, Birmingham (L.J.C.); Ohio State University Comprehensive Cancer Center, Columbus (A.M.K.); Janssen Research and Development, Raritan (N.L., J.M.S., C.C.J., K.C., T.Y., S.N.), and Legend Biotech, Somerset (E.F., L.P., N.P.) - both in New Jersey; Janssen, Buenos Aires (C.L.); Cilag International, Zug, Switzerland (A. Slaughter); Janssen Research and Development, Spring House, PA (K.L., E.Z.); Janssen China Research and Development, Shanghai (D.C.); and Universitätsklinikum Würzburg, Medizinische Klinik und Poliklinik II, Würzburg, Germany (H.E.).
Ciltacabtagene autoleucel (cilta-cel) significantly improved progression-free survival in patients with lenalidomide-refractory multiple myeloma. This CAR T-cell therapy demonstrated superior efficacy compared to standard care in earlier treatment lines.
Area of Science:
- Hematology
- Oncology
- Immunotherapy
Background:
- Ciltacabtagene autoleucel (cilta-cel) is a BCMA-directed CAR T-cell therapy effective in heavily pretreated multiple myeloma.
- Investigated cilta-cel in earlier treatment lines for patients with lenalidomide-refractory multiple myeloma.
Purpose of the Study:
- To evaluate the efficacy of cilta-cel compared to standard care in patients with lenalidomide-refractory multiple myeloma.
- To assess progression-free survival as the primary outcome in a phase 3 randomized trial.
Main Methods:
- Phase 3, randomized, open-label trial involving 419 patients with lenalidomide-refractory multiple myeloma.
- Patients received either cilta-cel or physician's choice of standard care after one to three previous treatment lines.
- Primary outcome was progression-free survival.
Main Results:
- Median progression-free survival was not reached with cilta-cel versus 11.8 months with standard care (HR, 0.26; P<0.001).
- 12-month progression-free survival was 75.9% for cilta-cel vs. 48.6% for standard care.
- Higher overall response (84.6% vs. 67.3%) and complete response or better (73.1% vs. 21.8%) rates observed with cilta-cel.
- Adverse events, including cytokine release syndrome and neurotoxicity, were reported, with most being low-grade.
Conclusions:
- A single cilta-cel infusion significantly reduced the risk of disease progression or death compared to standard care.
- Cilta-cel offers a more effective treatment option for lenalidomide-refractory multiple myeloma patients in earlier treatment settings.
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