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.
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 / Morabito, F.; Martino, E. A.; Galli, M.; Offidani, M.; Zambello, R.; Bringhen, S.; Giuliani, N.; Califano, C.; Brunori, M.; Gagliardi, A.; Sgherza, N.; Quinto, A. M.; Barila, G.; Belotti, A.; Cerchione, C.; Casaluci, G. M.; Fontana, R.; Bongarzoni, V.; Tarantini, G.; Derudas, D.; Patriarca, F.; Gozzetti, A.; Sementa, A.; Antonioli, E.; Rago, A.; Lotti, F.; De Magistris, C.; Petrucci, M. T.; Pettine, L.; Bolli, N.; Conticello, C.; Zamagni, E.; Palmieri, S.; Musso, M.; Mele, A.; Pepa, R. D.; Vigna, E.; Bruzzese, A.; Fazio, F.; Mina, R.; Paris, L.; Vincelli, I. D.; Farina, G.; Cangialosi, C.; Mancuso, K.; Falcone, A. P.; Mele, G.; Sica, A.; More, S.; Reddiconto, G.; Tripepi, G.; D'Arrigo, G.; Barbieri, E.; Quaresima, M.; Cartia, C. S.; Pezzatti, S.; Marcatti, M.; Farina, F.; Cafro, A.; Palumbo, M.; Masoni, V.; Ferretti, V. V.; Di Raimondo, F.; Musto, P.; Neri, A.; Mangiacavalli, S.; Gentile, M.. - In: EUROPEAN JOURNAL OF HAEMATOLOGY. - ISSN 0902-4441. - (2025). [10.1111/ejh.14413]
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
Giuliani N.;Brunori M.;Belotti A.;Antonioli E.;Lotti F.;Musso M.;Mele A.;Farina G.;Mele G.;Neri A.;
2025-01-01
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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
