Biallelic deletion of 1p32 defines ultra-high-risk myeloma, but monoallelic del(1p32) remains a strong prognostic factor

• Published in: Blood Vol. 141; no. 11; pp. 1308 - 1315
• Main Authors: Schavgoulidze, Anaïs, Talbot, Alexis, Perrot, Aurore, Cazaubiel, Titouan, Leleu, Xavier, Manier, Salomon, Buisson, Laure, Mahéo, Sabrina, Do Souto Ferreira, Laura, Pavageau, Luka, Hulin, Cyrille, Marolleau, Jean-Pierre, Voillat, Laurent, Belhadj, Karim, Divoux, Marion, Slama, Borhane, Brechignac, Sabine, Macro, Margaret, Stoppa, Anne-Marie, Sanhes, Laurence, Orsini-Piocelle, Frédérique, Fontan, Jean, Chretien, Marie-Lorraine, Demarquette, Hélène, Mohty, Mohamad, Avet-Loiseau, Hervé, Corre, Jill
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 16.03.2023; American Society of Hematology
• Subjects: Chromosome Aberrations; Human health and pathology; Humans; In Situ Hybridization, Fluorescence; Life Sciences; Multiple Myeloma - diagnosis; Multiple Myeloma - genetics; Prognosis; Progression-Free Survival
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.2022017863

•Del(1p32) is an independent and important adverse prognostic factor in myeloma.•Biallelic deletion of 1p32 dramatically worsens the prognosis compared with a monoallelic loss. [Display omitted] Cytogenetic abnormalities (CAs) are known to be the preponderant prognostic factor in multiple myeloma. Our team has recently developed a prognostic score based on 6 CAs, with which del(1p32) appears to be the second worst abnormality after del(17p). This study aimed to confirm the adverse effect of 1p32 deletion in patients with newly diagnosed multiple myeloma (NDMM). Among 2551 patients with newly diagnosed multiple myeloma, 11% were harboring del(1p32). Their overall survival (OS) was significantly inferior compared with patients without del(1p32) (median OS: 49 months vs 124 months). Likewise, progression-free survival was significantly shorter. More importantly, biallelic del(1p32) conferred a dramatically poorer prognosis than a monoallelic del(1p32) (median OS: 25 months vs 60 months). As expected, the OS of patients with del(1p32) significantly decreased when this abnormality was associated with other high-risk CAs [del(17p), t(4;14), or gain(1q)]. In the multivariate analysis, del(1p32) appeared as a negative prognostic factor; after adjustment for age and treatment, the risk of progression was 1.3 times higher among patients harboring del(1p32), and the risk of death was 1.9 times higher. At the dawn of risk-adapted treatment strategies, we have confirmed the adverse effect of del(1p32) in multiple myeloma and the relevance of its assessment at diagnosis. In this month’s CME article, Schavgoulidze et al confirm the adverse impact of 1p32 deletion in patients newly diagnosed with multiple myeloma (NDMM). In a study of 2551 patients with NDMM, the 11% harboring del(1p32) have inferior progression-free and overall survival (OS). Biallelic del(1p32) confirmed a dramatically worse prognosis, with a median OS of only 25 months. Detection of biallelic del(1p32) at diagnosis defines an ultra–high-risk subgroup of NDMM.