Morabito Fortunato, Martino Enrica Antonia, Galli Monica, Offidani Massimo, Zambello Renato, Bringhen Sara, Giuliani Nicola, Califano Catello, Brunori Marino, Gagliardi Alfredo, Sgherza Nicola, Quinto Angela Maria, Barilà Gregorio, Belotti Angelo, Cerchione Claudio, Casaluci Gloria Margiotta, Fontana Raffaele, Bongarzoni Velia, Tarantini Giuseppe, Derudas Daniele, Patriarca Francesca, Gozzetti Alessandro, Sementa Adelina, Antonioli Elisabetta, Rago Angela, Lotti Flavia, De Magistris Claudio, Petrucci Maria Teresa, Pettine Loredana, Bolli Niccolò, Conticello Concetta, Zamagni Elena, Palmieri Salvatore, Musso Maurizio, Mele Anna, Della Pepa Roberta, Vigna Ernesto, Bruzzese Antonella, Fazio Francesca, Mina Roberto, Paris Laura, Vincelli Iolanda Donatella, Farina Giuliana, Cangialosi Clotilde, Mancuso Katia, Falcone Antonietta Pia, Mele Giuseppe, Sica Antonello, Morè Sonia, Reddiconto Giovanni, Tripepi Giovanni, D'Arrigo Graziella, Barbieri Emiliano, Quaresima Micol, Cartia Claudio Salvatore, Pezzatti Sara, Marcatti Magda, Farina Francesca, Cafro Anna, Palumbo Michele, Masoni Valeria, Ferretti Virginia Valeria, Di Raimondo Francesco, Musto Pellegrino, Neri Antonino, Mangiacavalli Silvia, Gentile Massimo
Gruppo Amici Dell'Ematologia Foundation-GrADE, Reggio Emilia, Italy.
Hematology Unit AO of Cosenza, Cosenza, Italy.
Eur J Haematol. 2025 Jul;115(1):16-28. doi: 10.1111/ejh.14413. Epub 2025 Mar 19.
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.
关于+1q异常在真实世界环境中对复发/难治性多发性骨髓瘤(RRMM)影响的研究有限。本研究评估了1q获得性[gain(1q)]和扩增性[ampl(1q)]在635例接受基于达雷妥尤单抗、埃罗妥珠单抗和卡非佐米的三联方案治疗的RRMM患者中的预后和预测意义。与1q阴性患者的20.2%相比,存在+1q异常的患者深度缓解率较低[≥完全缓解(CR):gain(1q)为9.4%,ampl(1q)为11.6%]。多变量有序逻辑分析显示,gain(1q)(比值比[OR]=0.49,p<0.001)或ampl(1q)(OR=0.58,p=0.0037)的患者达到≥CR的几率显著降低。1q阴性患者的无进展生存期(PFS)更长(28个月),而gain(1q)(8个月)或ampl(1q)(7.4个月)的患者PFS较短。多变量模型确定gain(1q)(风险比[HR]=1.9,p<0.001)和ampl(1q)(HR=2.2,p<0.001)与del17p、t(4;14)、肌酐清除率<60 mL/min以及国际分期系统(ISS)II期和III期一样,是独立的不良预后因素。同样,gain(1q)(25个月)和ampl(1q)(19.5个月)的患者总生存期(OS)低于1q阴性患者的42.2个月。多变量分析显示gain(1q)(HR=1.6,p=0.007)和ampl(1q)(HR=2.0,p=0.002)是死亡率增加的独立预测因素。与高危细胞遗传学改变相关的辅助性+1q异常与较短的PFS和OS均相关。分层为无异常、单异常、双异常和三异常组显示出显著的生存差异,强调了累积细胞遗传学异常对预后的影响。总之,+1q异常对RRMM的预后有显著影响,应在风险分层中予以考虑。该研究强调了在真实世界环境中进行全面细胞遗传学分析的重要性,并突出了制定个性化治疗策略以改善患者预后的必要性。