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

Schavgoulidze, Anaïs; Talbot, Alexis; Perrot, Aurore; Cazaubiel, Titouan; Leleu, Xavier; Manier, Salomon; Buisson, Laure; Mahéo, Sabrina; Ferreira, Laura Do Souto; Pavageau, Luka; Hulin, Cyrille; Marolleau, Jean‐Pierre; Voillat, Laurent; Belhadj, Karim; Divoux, Marion; Slama, Borhane; Bréchignac, Sabine; Macro, Margaret; Stoppa, Anne Marie; Sanhès, Laurence; Piocelle, Frédérique Orsini; Fontan, Jean; Chrétien, Marie‐Lorraine; Demarquette, Hélène; Mohty, Mohamad; Avet-Loiseau, Hervé; Corre, Jill

doi:10.1182/blood.2022017863

Cited by 19 publications

(18 citation statements)

References 22 publications

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“…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.…”

Section: Discussionmentioning

confidence: 96%

“…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.…”

Section: Discussionmentioning

confidence: 99%

“…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)…”

Section: Discussionmentioning

confidence: 99%

“…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.…”

Section: Introductionmentioning

confidence: 99%

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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

Mohan

Gong²,

Ashby

et al. 2023

Cancer

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Background: Chromosome 1 abnormalities in multiple myeloma (MM) are increasingly recognized as high risk-defining features. The authors report the prognostic value of del(1p13.3) by fluorescence in situ hybridization (FISH) at enrollment in subjects treated on total therapy clinical trials 2-6.Methods: FISH probes were generated from specific BAC DNA clones for the AHCYL1 gene locus (1p13.3) and the CKS1B locus (1q21).Results: A total of 1133 patients were included in this analysis. Although del (1p13.3) was detected in 220 (19.4%) patients, 1q21gain or 1q21amp were observed in 300 (26.5%) and 150 (13.2%) patients, respectively. Concomitant del (1p13.3) with 1q21 gain or amp was observed in 65 (5.7%) and 29 (2.5%) patients, respectively. There was enrichment of high-risk features such as International Staging System (ISS) stage 3 disease and gene expression profiling (GEP)70 high risk (HR) in the group with del(1p13.3). Presence of del(1p13.3) confers inferior progression-free survival (PFS) and overall survival (OS). On multivariate analysis, the presence of ISS stage 3 disease, GEP70 HR, 1q21gain, and 1q21amp were independent predictors of PFS or OS. Conclusions:The PFS and OS of patients with combined abnormalities of del (1p13.3)/1q21gain or amp was significantly worse compared to del(1p13.3) alone and 1q21gain or 1q21 amp alone, which identifies a subset of patients with poor clinical outcomes.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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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

Mohan

Gong²,

Ashby

et al. 2023

Cancer

View full text Add to dashboard Cite

show abstract

“…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.…”

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confidence: 99%

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

Schmidt

2023

Cancer

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Making a case for del(1p) as a high-risk abnormality in multiple myelomaOver the past 2 decades, remarkable scientific and therapeutic discoveries have transformed multiple myeloma (MM) from a disease with few effective therapies and unacceptably high mortality to a condition that can often be successfully managed for years with a plethora of active treatments. However, despite this progress and nearly universal responses to initial therapy, MM is still largely considered an incurable disease. Although it is now commonplace for patients with MM to survive well beyond a decade, outcomes remain variable and some patients experience a more aggressive disease course. It is essential for clinicians to recognize biomarkers that might herald "high-risk" disease in order to set reasonable expectations with patients and to provide context for management decisions.One of the most powerful biomarkers in MM is the presence of recurrent chromosomal abnormalities within myeloma cells as detected by fluorescence in situ hybridization (FISH). Three chromosomal abnormalities-t(4;14), t(14;16), and del(17p)-were included in the Revised International Staging System (R-ISS), 1 reflecting that these abnormalities are often associated with high-risk disease. However, a variety of other factors known to affect prognosis are not included in the R-ISS. Chromosome 1 abnormalities (C1A), particularly copy gain and/or amplification (amp) of its long arm (+1q), are identified frequently in MM. Whereas amp(1q), defined as four or greater copies of the 1q locus, has been universally associated with worse outcomes, the prognostic impact of gain(1q), defined as three copies of the 1q locus, is debated. Nonetheless, due to its independent association with worse outcomes in several large data sets, +1q has been included as a high-risk abnormality in new proposed staging systems. [2][3][4] Deletions involving chromosome 1p are also commonly identified in MM, but the prognostic impact of del(1p)

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High‐risk multiple myeloma: Redefining genetic, clinical, and functional high‐risk disease in the era of molecular medicine and immunotherapy

Rees,

Kumar

2024

American J Hematol

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Multiple myeloma (MM) exhibits significant heterogeneity in its presentation, genetics, and treatment response. Despite therapeutic advances, some patients continue to relapse early (ER, <18‐months) and rapidly cycle through therapies. Myriad prognostic factors have been identified and incorporated into risk stratification models; however, these produce discordant, often three‐tiered outputs that fail to identify many patients destined for ER. Treatment strategies are increasingly focused on disease biology and trials enriched for high‐risk (HR)MM, but consensus on the minimum required testing and a succinct, specific, and clinically meaningful definition for HRMM remains elusive. We review the risk‐factors, definitions, and future directions for HRMM.

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

Cited by 19 publications

References 22 publications

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

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

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

High‐risk multiple myeloma: Redefining genetic, clinical, and functional high‐risk disease in the era of molecular medicine and immunotherapy

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