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.

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Journal
European Journal Of Haematology
Published
2025-03-19
DOI
https://doi.org/10.1111/ejh.14413
Citations
1
Primary Topic
Multiple Myeloma Research and Treatments
Type
article
Field-Weighted Citation Impact
1.77
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article

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

Giovanni Reddiconto, Concetta Conticello, Roberto Mina, Adelina Sementa et al.
1 citations
European Journal Of Haematology
Multiple Myeloma Research and Treatments
1.77
article

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

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

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.

European Journal Of HaematologyVol. 115(1)
University of Siena (IT), University of Modena and Reggio Emilia (IT), Università degli Studi del Piemonte Orientale “Amedeo Avogadro” (IT), University of Parma (IT), University of Udine (IT), University of Padua (IT), Vita-Salute San Raffaele University (IT), University of Cagliari (IT), University of Pavia (IT), Azienda Ospedaliera San Giovanni Addolorata (IT), Casa Sollievo della Sofferenza (IT), Policlinico Umberto I (IT), CTO Hospital (IT), Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (IT), University of Catania (IT), Azienda Ospedaliera Citta' della Salute e della Scienza di Torino (IT), Azienda Ospedaliera di Perugia (IT), Azienda Sanitaria Unità Locale di Reggio Emilia (IT), ASL Roma (IT), Ospedale Santa Maria di Loreto Nuovo (IT), Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IT), Azienda ospedaliera "Bianchi-Melacrino-Morelli" (IT), Ospedale Santa Maria alle Scotte (IT), Ospedale Vincenzo Cervello (IT), Azienda Ospedaliera di Cosenza (IT), Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia (IT), Ospedale A. Perrino (IT), Ospedale Papa Giovanni XXIII (IT), Ospedali Riuniti di Ancona (IT), Azienda Ospedaliera San Gerardo (IT), Azienda Ospedaliero-Universitaria Careggi (IT), Ospedale Santa Maria (IT), Federico II University Hospital (IT), Istituto di Ematologia di Bologna (IT), Policlinico Universitario di Catania (IT), Istituto Tumori Bari (IT), Ospedali Riuniti San Giovanni di Dio e Ruggi d'Aragona (IT), Ospedale San Giuseppe (IT), Ospedale Sant'Anna (IT), Policlinico San Matteo Fondazione (IT), Ospedale San Bortolo (IT), Ospedale Vito Fazzi (IT), Istituti di Ricovero e Cura a Carattere Scientifico (IT), Azienda Sanitaria Locale Roma 3 (IT), Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele (IT), University of Calabria (IT), University of Bari Aldo Moro (IT), Sapienza University of Rome (IT), University of Bologna (IT)
Openalex Percentile: Top 18%
Multiple Myeloma Research and Treatments
1.77
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