Prognostic Significance of +1q Alterations in Relapsed/Refractory Multiple Myeloma Treated With Daratumumab-, Elotuzumab-, and Carfilzomib-Based Triplet Regimens: A Multicenter Real-World Analysis of 635 Patients.

Journal: European Journal Of Haematology

Published: January 31, 2025

Abstract

Relapsed/refractory multiple myeloma (RRMM) research on the impact of +1q abnormalities in real-world settings is limited. This study evaluated the prognostic and predictive significance of 1q gain [gain(1q)] and amplification [ampl(1q)] in 635 RRMM patients treated with daratumumab-, elotuzumab-, and carfilzomib-based triplet regimens. Patients with +1q abnormalities had lower deep response rates [≥ CR: 9.4% for gain(1q), 11.6% for ampl(1q)] versus 20.2% in +1q-negative patients. Multivariable ordinal logistic analysis showed significantly lower odds of achieving ≥ CR in patients with gain(1q) (OR = 0.49, p < 0.001) or ampl(1q) (OR = 0.58, p = 0.0037). Progression-free survival (PFS) was longer in +1q-negative patients (28 months) compared to those with gain(1q) (8 months) or ampl(1q) (7.4 months). Multivariable models identified gain(1q) (HR = 1.9, p < 0.001) and ampl(1q) (HR = 2.2, p < 0.001) as independent negative prognostic factors alongside del17p, t(4;14), creatinine clearance < 60 mL/min, and ISS Stages II and III. Similarly, overall survival (OS) was reduced for patients with gain(1q) (25 months) and ampl(1q) (19.5 months) versus 42.2 months in +1q-negative patients. Multivariable analysis showed gain(1q) (HR = 1.6, p = 0.007) and ampl(1q) (HR = 2.0, p = 0.002) as independent predictors of increased mortality. Ancillary +1q abnormalities associated with high-risk cytogenetic changes were linked to both shorter PFS and OS. Stratification into no-hit, single-hit, double-hit, and triple-hit groups showed significant survival differences, emphasizing the impact of cumulative cytogenetic abnormalities on outcomes. In conclusion, +1q abnormalities significantly impact prognosis in RRMM and should be considered in risk stratification. The study emphasizes the importance of comprehensive cytogenetic profiling in real-world settings and highlights the need for personalized treatment strategies to improve patient outcomes.

Authors

Fortunato Morabito, Enrica Martino, Monica Galli, Massimo Offidani, Renato Zambello, Sara Bringhen, Nicola Giuliani, Catello Califano, Marino Brunori, Alfredo Gagliardi, Nicola Sgherza, Angela Quinto, Gregorio Barilà, Angelo Belotti, Claudio Cerchione, Gloria Casaluci, Raffaele Fontana, Velia Bongarzoni, Giuseppe Tarantini, Daniele Derudas, Francesca Patriarca, Alessandro Gozzetti, Adelina Sementa, Elisabetta Antonioli, Angela Rago, Flavia Lotti, Claudio De Magistris, Maria Petrucci, Loredana Pettine, Niccolò Bolli, Concetta Conticello, Elena Zamagni, Salvatore Palmieri, Maurizio Musso, Anna Mele, Roberta Della Pepa, Ernesto Vigna, Antonella Bruzzese, Francesca Fazio, Roberto Mina, Laura Paris, Iolanda Vincelli, Giuliana Farina, Clotilde Cangialosi, Katia Mancuso, Antonietta Falcone, Giuseppe Mele, Antonello Sica, Sonia Morè, Giovanni Reddiconto, Giovanni Tripepi, Graziella D'arrigo, Emiliano Barbieri, Micol Quaresima, Claudio Cartia, Sara Pezzatti, Magda Marcatti, Francesca Farina, Anna Cafro, Michele Palumbo, Valeria Masoni, Virginia Ferretti, Francesco Di Raimondo, Pellegrino Musto, Antonino Neri, Silvia Mangiacavalli, Massimo Gentile

Relevant Conditions

Hypertension, Multiple Myeloma

Prognostic Significance of +1q Alterations in Relapsed/Refractory Multiple Myeloma Treated With Daratumumab-, Elotuzumab-, and Carfilzomib-Based Triplet Regimens: A Multicenter Real-World Analysis of 635 Patients.

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