Remission conversion drives outcomes after CAR T-cell therapy for multiple myeloma: a registry analysis from the DRST
Abstract
Abstract Cellular therapies targeting B-cell maturation antigen have shown promise in controlled clinical trials, but their impact in broader, diverse patient populations remains underexplored. This study examines the real-world efficacy and safety in 343 triple-class–exposed patients with relapsed and refractory multiple myeloma who received idecabtagene vicleucel (ide-cel; n = 266) or ciltacabtagene autoleucel (cilta-cel; n = 77) after >3 previous lines of therapy in Germany. Cilta-cel, compared with ide-cel, demonstrated superior outcomes, achieving a higher overall response rate (94% vs 82%) and 10-month progression-free survival (PFS; 76% vs 47%). Cilta-cel also led to higher complete response (CR; 61% vs 39%) and improved response conversion, with more patients achieving CR after starting from less than CR before chimeric antigen receptor T-cell (CAR T) therapy. For those attaining CR after therapy, cilta-cel showed longer PFS, especially in patients who entered treatment with a partial response or worse. Cytokine release syndrome was observed in 85% of cilta-cel and 81% of ide-cel cases, predominantly low grade. Immune effector cell–associated neurotoxicity syndrome was more common with cilta-cel (25% vs 15%), although nonrelapse mortality at 10 months was comparable between therapies (7% vs 5%). Weighted multivariable analysis after propensity score matching confirmed a significant advantage in terms of PFS for cilta-cel, with a hazard ratio of 0.48. Overall, outcomes in our registry analysis were comparable with the pivotal trials that led to approval of the respective agents. Cilta-cel demonstrated a greater capacity for response conversion and durable remission. These findings underscore the need for individualized CAR T therapy selection to optimize patient outcomes.
Article Details
Authors (25)
Maximilian Merz
11Myeloma Service, Memorial Sloan Kettering Cancer Center, New York, NY
Nico Gagelmann
From the Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Samih Smaili
4German Registry for Stem Cell Transplantation, Deutsches Register für hämatopoetische Stammzelltransplantation und Zelltherapie, Ulm, Germany
Sarah Flossdorf
4German Registry for Stem Cell Transplantation, Deutsches Register für hämatopoetische Stammzelltransplantation und Zelltherapie, Ulm, Germany
Sandra Sauer
Christof Scheid
12Hospital Barmherzige Brueder Regensburg, Clinic for Oncology and Hematology, Regensburg, Germany
Bastian von Tresckow
1Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Department I of Internal Medicine, Faculty of Medicine and University Hospital of Cologne, University of Cologne, and German Hodgkin Study Group, Cologne, Germany
Gerald Wulf
1University Medical Center Göttingen, Department of Hematology and Medical Oncology, Göttingen, Germany
Katja Weisel
Igor Wolfgang Blau
14Charité University Medicine Berlin, Medical Clinic, Berlin, Germany
Monika Engelhardt
Ralph Wäsch
18Department of Medicine I, Hematology, Oncology and Stem Cell Transplantation, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany
Natalie Schub
5UKSH, Kiel, Germany
Raphael Teipel
Department of Internal Medicine I, University Hospital Dresden, Technical University Dresden, Dresden, Germany
Judith Hecker
1Technical University of Munich (TUM), Klinikum rechts der Isar, School of Medicine and Health, Department of Medicine III, Munich, Germany
Johannes Waldschmidt
5Department of Medicine II, University Hospital Würzburg, Würzburg, Germany
Britta Besemer
Department of Internal Medicine II, University Tübingen, Tübingen, Germany
Ben-Niklas Baermann
Simon Call
1University Hospital Muenster, Department of Medicine A, Hematology, Oncology and Pneumology, Muenster, Germany
Leo Hansmann
2University Hospital Regensburg, Department of Internal Medicine III, Hematology & Internal Oncology, Regensburg, Germany
Francis Ayuketang Ayuk
3Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Marc S. Raab
Hermann Einsele
Uwe Platzbecker
Nicolaus Kröger
From the Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.