Fortunato Morabito, Enrica Antonia Martino, Monica Galli, Massimo Offidani, Renato Zambello, Sara Bringhen, Nicola Giuliani, Catello Califano, Marino Brunori, Alfredo Gagliardi, Nicola Sgherza, Angela Maria Quinto, Gregorio Barilà, Angelo Belotti, Claudio Cerchione, Gloria Margiotta 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 Teresa 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 Donatella Vincelli, Giuliana Farina, Clotilde Cangialosi, Katia Mancuso, Antonietta Pia Falcone, Giuseppe Mele, Antonello Sica, Sonia Morè, Giovanni Reddiconto, Giovanni Tripepi, Graziella D'Arrigo, Emiliano Barbieri, Micol Quaresima, Claudio Salvatore Cartia, Sara Pezzatti, Magda Marcatti, Francesca Farina, Anna Cafro, Michele Palumbo, Valeria Masoni, Virginia Valeria Ferretti, Francesco Di Raimondo, Pellegrino Musto, Antonino Neri, Silvia Mangiacavalli, Massimo Gentile
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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.</p>","PeriodicalId":11955,"journal":{"name":"European Journal of Haematology","volume":" ","pages":""},"PeriodicalIF":2.3000,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"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.\",\"authors\":\"Fortunato Morabito, Enrica Antonia Martino, Monica Galli, Massimo Offidani, Renato Zambello, Sara Bringhen, Nicola Giuliani, Catello Califano, Marino Brunori, Alfredo Gagliardi, Nicola Sgherza, Angela Maria Quinto, Gregorio Barilà, Angelo Belotti, Claudio Cerchione, Gloria Margiotta 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 Teresa 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 Donatella Vincelli, Giuliana Farina, Clotilde Cangialosi, Katia Mancuso, Antonietta Pia Falcone, Giuseppe Mele, Antonello Sica, Sonia Morè, Giovanni Reddiconto, Giovanni Tripepi, Graziella D'Arrigo, Emiliano Barbieri, Micol Quaresima, Claudio Salvatore Cartia, Sara Pezzatti, Magda Marcatti, Francesca Farina, Anna Cafro, Michele Palumbo, Valeria Masoni, Virginia Valeria Ferretti, Francesco Di Raimondo, Pellegrino Musto, Antonino Neri, Silvia Mangiacavalli, Massimo Gentile\",\"doi\":\"10.1111/ejh.14413\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Relapsed/refractory multiple myeloma (RRMM) research on the impact of +1q abnormalities in real-world settings is limited. 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引用次数: 0
摘要
复发/难治性多发性骨髓瘤（RRMM）对+1q异常在现实环境中的影响的研究是有限的。本研究评估了635例接受达拉单抗、埃妥珠单抗和卡非佐米三联方案治疗的RRMM患者的1q增益[gain(1q)]和扩增[ampl(1q)]的预后和预测意义。+1q异常患者的深度缓解率较低[≥CR: gain(1q) 9.4%, ampl(1q) 11.6%]，而+1q阴性患者的深度缓解率为20.2%。多变量有序逻辑分析显示，获得（1q）的患者达到≥CR的几率显著降低(OR = 0.49, p
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.
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.
期刊介绍：
European Journal of Haematology is an international journal for communication of basic and clinical research in haematology. The journal welcomes manuscripts on molecular, cellular and clinical research on diseases of the blood, vascular and lymphatic tissue, and on basic molecular and cellular research related to normal development and function of the blood, vascular and lymphatic tissue. The journal also welcomes reviews on clinical haematology and basic research, case reports, and clinical pictures.
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