Development and Validation of a Prediction Model of Outcome After B-Cell Maturation Antigen-Directed Chimeric Antigen Receptor T-Cell Therapy in Relapsed/Refractory Multiple Myeloma.

Autor:	Gagelmann N; Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Dima D; Cleveland Clinic Taussig Cancer Center, Cleveland, OH.; US Myeloma Innovations Research Collaborative (USMIRC), Kansas City, KS., Merz M; Department of Hematology, Cellular Therapy, Hemostaseology and Infectiology, University Hospital of Leipzig, Leipzig, Germany., Hashmi H; US Myeloma Innovations Research Collaborative (USMIRC), Kansas City, KS.; Medical University of South Carolina, Charleston, SC., Ahmed N; US Myeloma Innovations Research Collaborative (USMIRC), Kansas City, KS.; The University of Kansas Medical Center, Kansas City, KS., Tovar N; Hospital Clínic de Barcelona, IDIBAPS, University of Barcelona, Barcelona, Spain., Oliver-Caldés A; Hospital Clínic de Barcelona, IDIBAPS, University of Barcelona, Barcelona, Spain., Stölzel F; Division for Stem Cell Transplantation and Cellular Immunotherapy, Department of Medicine II, University Hospital Schleswig-Holstein Kiel, Kiel University, Kiel, Germany., Rathje K; Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Fischer L; Department of Hematology, Cellular Therapy, Hemostaseology and Infectiology, University Hospital of Leipzig, Leipzig, Germany., Born P; Department of Hematology, Cellular Therapy, Hemostaseology and Infectiology, University Hospital of Leipzig, Leipzig, Germany., Schäfer L; Department of Hematology and Medical Oncology, Medical Center University of Göttingen, Göttingen, Germany., Albici AM; Division for Stem Cell Transplantation and Cellular Immunotherapy, Department of Medicine II, University Hospital Schleswig-Holstein Kiel, Kiel University, Kiel, Germany., Schub N; Division for Stem Cell Transplantation and Cellular Immunotherapy, Department of Medicine II, University Hospital Schleswig-Holstein Kiel, Kiel University, Kiel, Germany., Kfir-Erenfeld S; Department of Bone Marrow Transplantation and Cancer Immunotherapy, Faculty of Medicine, Hadassah Medical Center, Hebrew University of Jerusalem, Jerusalem, Israel., Assayag M; Department of Bone Marrow Transplantation and Cancer Immunotherapy, Faculty of Medicine, Hadassah Medical Center, Hebrew University of Jerusalem, Jerusalem, Israel., Asherie N; Department of Bone Marrow Transplantation and Cancer Immunotherapy, Faculty of Medicine, Hadassah Medical Center, Hebrew University of Jerusalem, Jerusalem, Israel., Wulf GG; Department of Hematology and Medical Oncology, Medical Center University of Göttingen, Göttingen, Germany., Kharboutli S; Department of Internal Medicine, Haematology and Oncology, University Hospital of Erlangen, Friedrich-Alexander University of Erlangen-Nuremberg (FAU), Erlangen, Germany., Müller F; Department of Internal Medicine, Haematology and Oncology, University Hospital of Erlangen, Friedrich-Alexander University of Erlangen-Nuremberg (FAU), Erlangen, Germany., Shune L; US Myeloma Innovations Research Collaborative (USMIRC), Kansas City, KS.; The University of Kansas Medical Center, Kansas City, KS., Davis JA; US Myeloma Innovations Research Collaborative (USMIRC), Kansas City, KS.; Medical University of South Carolina, Charleston, SC., Anwer F; Cleveland Clinic Taussig Cancer Center, Cleveland, OH.; US Myeloma Innovations Research Collaborative (USMIRC), Kansas City, KS., Vucinic V; Department of Hematology, Cellular Therapy, Hemostaseology and Infectiology, University Hospital of Leipzig, Leipzig, Germany., Platzbecker U; Department of Hematology, Cellular Therapy, Hemostaseology and Infectiology, University Hospital of Leipzig, Leipzig, Germany., Ayuk F; Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Kröger N; Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Khouri J; Cleveland Clinic Taussig Cancer Center, Cleveland, OH., Gurnari C; Cleveland Clinic Taussig Cancer Center, Cleveland, OH.; Department of Biomedicine and Prevention, PhD in Immunology, Molecular Medicine and Applied Biotechnology, University of Rome Tor Vergata, Rome, Italy., McGuirk J; US Myeloma Innovations Research Collaborative (USMIRC), Kansas City, KS.; The University of Kansas Medical Center, Kansas City, KS., Stepensky P; Department of Bone Marrow Transplantation and Cancer Immunotherapy, Faculty of Medicine, Hadassah Medical Center, Hebrew University of Jerusalem, Jerusalem, Israel., Abdallah AO; US Myeloma Innovations Research Collaborative (USMIRC), Kansas City, KS.; The University of Kansas Medical Center, Kansas City, KS., Fernández de Larrea C; Hospital Clínic de Barcelona, IDIBAPS, University of Barcelona, Barcelona, Spain.
Jazyk:	angličtina
Zdroj:	Journal of clinical oncology : official journal of the American Society of Clinical Oncology [J Clin Oncol] 2024 May 10; Vol. 42 (14), pp. 1665-1675. Date of Electronic Publication: 2024 Feb 15.
DOI:	10.1200/JCO.23.02232
Abstrakt:	Purpose: Although chimeric antigen receptor T therapy (CAR-T) cells are an established therapy for relapsed/refractory multiple myeloma (RRMM), there are no established models predicting outcome to identify patients who may benefit the most from CAR-T. Patients and Methods: This is an international retrospective observational study including patients with RRMM infused with currently available commercial or academically produced anti-B-cell maturation antigen (BCMA) CAR-T. We describe characteristics and outcomes in Europe (n = 136) and the United States (n = 133). Independent predictors of relapse/progression built a simple prediction model (Myeloma CAR-T Relapse [MyCARe] model) in the training cohort (Europe), which was externally validated (US cohort) and tested within patient- and treatment-specific subgroups. Results: The overall response rate was 87% and comparable between both cohorts, and complete responses were seen in 48% (Europe) and 49% (the United States). The median time to relapse was 5 months, and early relapse <5 months from infusion showed poor survival across cohorts, with the 12-month overall survival of 30% (Europe) and 14% (the United States). The presence of extramedullary disease or plasma cell leukemia, lenalidomide-refractoriness, high-risk cytogenetics, and increased ferritin at the time of lymphodepletion were independent predictors of early relapse or progression. Each factor received one point, forming the three-tiered MyCARe model: scores 0-1 (low risk), scores 2-3 (intermediate risk), and a score of 4 (high risk). The MyCARe model was significantly associated with distinct 5-month incidence of relapse/progression ( P < .001): 7% for low-risk, 27% for intermediate-risk, and 53% for high-risk groups. The model was validated in the US cohort and maintained prognostic utility for response, survival, and outcomes across subgroups. Conclusion: Outcomes of patients with RRMM after CAR-T are comparable between Europe and the United States. The MyCARe model may facilitate optimal timing of CAR-T cells in patient-specific subgroups.
Databáze:	MEDLINE
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