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

Abstract

Cytogenetics abnormalities (CA) are known to be the preponderant prognostic factor in multiple myeloma (MM). Our team has recently developed a prognostic score based on 6 CA, where del(1p32) appears to be the second worst abnormality after del(17p). The aim of this study was to confirm the adverse impact of 1p32 deletion on newly-diagnosed multiple myeloma (NDMM) patients. Among 2551 NDMM patients, 11% were harboring del(1p32). Their overall survival (OS) was significantly inferior compared to 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 del(1p32) patients significantly decreased when this abnormality was associated with other high-risk CA (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 impact of del(1p32) in MM and the relevance of its assessment at diagnosis.

Concomitant deletion of the short arm (del(1p13.3)) and amplification or gain (1q21) of chromosome 1 by fluorescence in situ hybridization are associated with a poor clinical outcome in multiple myeloma

“…These factors could possibly explain the statistical significance of del(1p32) in PFS and OS noted in this study. 14 In another recent report of post hoc analysis of NDMM patients treated on the Eastern Cooperative Oncology Group E1A11 study, the presence of del 1p was associated an inferior PFS and OS. 28 In this study, treatment with carfilzomib, lenalidomide, and dexamethasone, but not Bortezomib, lenalidomide, dexamethasone abrogates adverse outcomes conferred by del 1p.…”

“…When cases with deletions and mutations of the FAM46C gene were taken together, they were associated with impaired OS 13 . In a recent report of 2551 newly diagnosed multiple myeloma (NDMM) patients, the OS of patients with biallelic del(1p32) was particularly worse at 25 months compared to 60 months with monoallelic del(1p32) 14 . Additionally, the outcomes were inferior when del(1p32) was associated with high‐risk cytogenetic abnormalities such as (del(17p), t(4;14), or 1q gain.…”

“…13 In a recent report of 2551 newly diagnosed multiple myeloma (NDMM) patients, the OS of patients with biallelic del(1p32) was particularly worse at 25 months compared to 60 months with monoallelic del(1p32). 14 Additionally, the outcomes were inferior when del(1p32) was associated with high-risk cytogenetic abnormalities such as (del(17p), t(4;14), or 1q gain. In contrast to our analysis, this study includes del(1p32)…”

“…12 In MM, the interstitial deletion could involve different regions on 1p, including 1p32.3, 1p31.3, 1p22.1-1p21.3, and 1p12. 13,14 Clinical implication of del (1p) status varies with specific regional loss and has been associated with shorter survival in transplant-eligible patients. 12,13,15,16 We hereby report the prognostic value of del(1p13.…”

Making a case for del(1p) as a high‐risk abnormality in multiple myeloma

“…In fact, these results appear to be consistent with and complement the existing literature regarding the prognostic impact of del(1p) in the modern era of MM management. In addition to several historical data sets that showed poor outcomes for patients with del(1p), [12][13][14][15][16] a retrospective analysis from the Intergroupe Francophone du Myélome 17 and a post hoc analysis of the Eastern Cooperative Oncology Group E1A11 trial 18 both found that patients with del(1p) was associated with worse outcomes among patients treated with modern induction regimens.…”