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
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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. / Gagelmann, Nico; Dima, Danai; Merz, Maximilian; Hashmi, Hamza; Ahmed, Nausheen; Tovar, Natalia; Oliver-Caldés, Aina; Stölzel, Friedrich; Rathje, Kristin; Fischer, Luise; Born, Patrick; Schäfer, Lisa; Albici, Anca-Maria; Schub, Natalie; Kfir-Erenfeld, Shlomit; Assayag, Miri; Asherie, Nathalie; Wulf, Gerald Georg; Kharboutli, Soraya; Müller, Fabian; Shune, Leyla; Davis, James A; Anwer, Faiz; Vucinic, Vladan; Platzbecker, Uwe; Ayuk, Francis; Kröger, Nicolaus; Khouri, Jack; Gurnari, Carmelo; McGuirk, Joseph; Stepensky, Polina; Abdallah, Al-Ola; Fernández de Larrea, Carlos.
in: J CLIN ONCOL, Jahrgang 42, Nr. 14, 10.05.2024, S. 1665-1675.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - 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
AU - Gagelmann, Nico
AU - Dima, Danai
AU - Merz, Maximilian
AU - Hashmi, Hamza
AU - Ahmed, Nausheen
AU - Tovar, Natalia
AU - Oliver-Caldés, Aina
AU - Stölzel, Friedrich
AU - Rathje, Kristin
AU - Fischer, Luise
AU - Born, Patrick
AU - Schäfer, Lisa
AU - Albici, Anca-Maria
AU - Schub, Natalie
AU - Kfir-Erenfeld, Shlomit
AU - Assayag, Miri
AU - Asherie, Nathalie
AU - Wulf, Gerald Georg
AU - Kharboutli, Soraya
AU - Müller, Fabian
AU - Shune, Leyla
AU - Davis, James A
AU - Anwer, Faiz
AU - Vucinic, Vladan
AU - Platzbecker, Uwe
AU - Ayuk, Francis
AU - Kröger, Nicolaus
AU - Khouri, Jack
AU - Gurnari, Carmelo
AU - McGuirk, Joseph
AU - Stepensky, Polina
AU - Abdallah, Al-Ola
AU - Fernández de Larrea, Carlos
PY - 2024/5/10
Y1 - 2024/5/10
N2 - 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.
AB - 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.
U2 - 10.1200/JCO.23.02232
DO - 10.1200/JCO.23.02232
M3 - SCORING: Journal article
C2 - 38358946
VL - 42
SP - 1665
EP - 1675
JO - J CLIN ONCOL
JF - J CLIN ONCOL
SN - 0732-183X
IS - 14
ER -