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Table 1.  

 

Patients with del(1p32)

Patients without del(1p32)

P value

Patients, n 282 2269  
Age at diagnosis, mean (SD), y 63.8 (10.8) 63.6 (10.7) .9876
Sex, n (%)     .6655
Male 169 (59.9) 1323 (58.4)  
Female 113 (40.1) 943 (41.6)  
Missing 0 3  
ISS, n (%)     .0177
1 48 (21.7) 540 (29.2)  
2 94 (42.5) 795 (42.9)  
3 79 (35.7) 517 (27.9)  
Patients, n 221 1852  
Missing, n 61 417  
Del(17p), n (%)     <.0001
No 217 (77.5) 2064 (91.2)  
Yes 63 (22.5) 199 (8.8)  
Missing 2 6  
t(4;14), n (%)     .8478
No 245 (88.4) 1966 (87.8)  
Yes 32 (11.6) 272 (12.2)  
Missing 5 31  
Gain(1q), n (%)     <.0001
No 127 (45.0) 1502 (66.2)  
Yes 155 (55.0) 766 (33.8)  
Missing 0 1  
t(14;16), n (%)     .0016
No 91 (87.5) 689 (95.6)  
Yes 13 (12.5) 32 (4.4)  
Missing 178 1,548  
t(14;20), n (%)     .6969
No 67 (98.5) 301 (96.8)  
Yes 1 (1.5) 10 (3.2)  
Missing 214 1,958  
TP53 mutation, n (%)     .0010
No 55 (72.4) 288 (88.1)  
Yes 21 (27.6) 39 (11.9)  
Missing 206 1,942  
Hyperdiploidy (>50 chromosomes), n (%)     .0065
No 188 (69.9) 1336 (61.1)  
Yes 81 (30.1) 849 (38.9)  
Missing 13 84  
First-line therapy, n (%)      
Patients eligible for transplant      
IMiD or PI without anti-CD38 20 (14.9) 178 (15.8) .1061
Triplet * 104 (77.6) 905 (80.6)  
Triplet + anti-CD38 10 (7.5) 41 (3.6)  
Patients not eligible for transplant      
IMiD or PI without anti-CD38 84 (59.2) 716 (64.0) .0819
IMiD or PI with anti-CD38 11 (7.7) 41 (3.7)  
Triplet 44 (31.0) 350 (31.3)  
Triplet + anti-CD38 3 (2.1) 12 (1.0)  
Missing 6 26  
Maintenance therapy for patients eligible for transplant, n (%)     .3161
No 77 (57.5) 696 (61.9)  
Yes 57 (42.5) 428 (38.1)  
Missing 0 0  

Table 1. Characteristics of patients according to deletion-1p32 status

IMiDs, immunomodulatory drugs; ISS, International Staging System; PI, proteasome inhibitors; SD, standard deviation.

*Triplet is defined by the association of 1 IMiD, 1 PI, and 1 corticosteroid (mostly dexamethasone).

Table 2.  

Variable

Univariate analysis

Multivariate analysis

PFS (n = 1860)

OS (n = 1721 )

PFS (n = 1860)

OS (n = 1721)

HR (95% CI)

P value

HR (95% CI)

P value

HR (95% CI)

P value

HR (95% CI)

P value

Age 1.0 (1.0-1.0) <.0001 1.0 (1.0-1.0) <.0001        
High-dose melphalan 1.7 (1.6-1.9) <.0001 1.6 (1.4-1.) <.0001        
ISS II vs I 1.4 (1.3-1.6) <.0001 1.9 (1.5-2.4) <.0001 1.2 (1.1-1.4) .0016 1.5 (1.2-1.8) .001
ISS III vs I 2.0 (1.7-2.3) <.0001 2.9 (2.3-3.6) <.0001 1.7 (1.5-2.0) <.0001 2.1 (1.6-2.6) <.0001
del(1p32) 1.5 (1.2-1.7) <.0001 2.5 (2.0-3.1) <.0001 1.3 (1.1-1.5) .0065 1.9 (1.5-2.40) <.0001
del(17p) 1.9 (1.6-2.2) <.0001 3.2 (2.6-3.9) <.0001 1.8 (1.5-2.1) <.0001 2.9 (2.3-3.8) <.0001
t(4;14) 1.6 (1.4-1.8) <.0001 2.2 (1.8-2.7) <.0001 1.4 (1.2-1.7) <.0001 1.7 (1.4-2.2) <.0001
Gain(1q) 1.5 (1.3-1.6) <.0001 1.9 (1.7-2.3) <.0001 1.3 (1.2-1.5) <.0001 1.6 (1.3-1.9) <.0001

Table 2. Univariate and multivariate analyses for PFS and OS

CI, confidence interval; HR, hazard ratio; OS, overall survival; PFS, progression-free survival.

CME / ABIM MOC

Biallelic Deletion of 1p32 Defines Ultra-High-Risk Myeloma, but Monoallelic del(1p32) Remains a Strong Prognostic Factor

  • Authors: Anaïs Schavgoulidze, PharmD; Alexis Talbot, MD; Aurore Perrot, MD, PhD; Titouan Cazaubiel, MD; Xavier Leleu, MD; Salomon Manier, MD, PhD; Laure Buisson, MsC; Sabrina Mahéo, MsC; Laura Do Souto Ferreira, MsC; Luka Pavageau, MsC; Cyrille Hulin, MD; Jean-Pierre Marolleau, MD; Laurent Voillat, MD; Karim Belhadj, MD; Marion Divoux, MD; Borhane Slama, MD; Sabine Brechignac, MD; Margaret Macro, MD; Anne-Marie Stoppa, MD; Laurence Sanhes, MD; Frédérique Orsini-Piocelle, MD; Jean Fontan, MD; Marie-Lorraine Chretien, MD, PhD; Hélène Demarquette, MD; Mohamad Mohty, MD; Hervé Avet-Loiseau, MD, PhD; Jill Corre, PharmD, PhD
  • CME / ABIM MOC Released: 3/16/2023
  • Valid for credit through: 3/16/2024, 11:59 PM EST
Start Activity

  • Credits Available

    Physicians - maximum of 1.00 AMA PRA Category 1 Credit(s)™

    ABIM Diplomates - maximum of 1.00 ABIM MOC points

    You Are Eligible For

    • Letter of Completion
    • ABIM MOC points

Target Audience and Goal Statement

This activity is intended for hematologists, oncologists, internists, geneticists, and other physicians caring for patients with newly diagnosed multiple myeloma (NDMM).

The goal of this activity is for learners to be better able to describe the impact of 1p32 deletion, or del(1p32), on patients with NDMM, according to a study using a prognostic score developed from 6 cytogenetic abnormalities (CAs).

Upon completion of this activity, participants will:

  • Have increased knowledge regarding the
    • Impact of monoallelic and biallelic del(1p32) on overall survival and progression-free survival among patients with newly diagnosed multiple myeloma (NDMM)
    • Prognostic value of other high-risk cytogenetic abnormalities (CAs) in combination with del(1p32) among patients with NDMM, according to a study using a prognostic score developed from 6 CAs
    • Clinical implications of the impact of del(1p32) on patients with NDMM


Disclosures

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Faculty

  • Anaïs Schavgoulidze, PharmD

    Unit for Genomics in Myeloma
    University Hospital IUC-Oncopole and Toulouse Cancer Research Center-Oncopole
    Toulouse University
    Inserm UMR1037
    Toulouse, France

  • Alexis Talbot, MD

    Hematology Department
    Saint-Louis University Hospital
    University of Paris
    AP-HP
    Paris, France

  • Aurore Perrot, MD, PhD

    Hematology Department
    University Hospital IUC-Oncopole and Toulouse Cancer Research Center-Oncopole
    Toulouse, France

  • Titouan Cazaubiel, MD

    Hematology Department
    Bordeaux University Hospital
    Bordeaux, France

  • Xavier Leleu, MD

    Hematology Department
    Poitiers University Hospital
    Poitiers, France

  • Salomon Manier, MD, PhD

    Hematology Department
    Lille University Hospital
    Lille, France

  • Laure Buisson, MsC

    Unit for Genomics in Myeloma
    University Hospital IUC-Oncopole and Toulouse Cancer Research Center-Oncopole
    Toulouse University
    Inserm UMR1037
    Toulouse, France

  • Sabrina Mahéo, MsC

    Unit for Genomics in Myeloma
    University Hospital IUC-Oncopole and Toulouse Cancer Research Center-Oncopole
    Toulouse University
    Inserm UMR1037
    Toulouse, France

  • Laura Do Souto Ferreira, MsC

    Unit for Genomics in Myeloma, University Hospital IUC-Oncopole and Toulouse Cancer Research Center-Oncopole
    Toulouse University
    Inserm UMR1037
    Toulouse, France

  • Luka Pavageau, MsC

    Unit for Genomics in Myeloma
    University Hospital IUC-Oncopole and Toulouse Cancer Research Center-Oncopole
    Toulouse University
    Inserm UMR1037
    Toulouse, France

  • Cyrille Hulin, MD

    Hematology Department
    Bordeaux University Hospital
    Bordeaux, France

  • Jean-Pierre Marolleau, MD

    Hematology Department
    Amiens University Hospital
    Amiens, France

  • Laurent Voillat, MD

    Hematology Department
    Chalon-sur-Saône Hospital
    Chalon-sur-Saône, France

  • Karim Belhadj, MD

    Hematology Department
    Créteil University Hospital
    Créteil, France

  • Marion Divoux, MD

    Hematology Department
    Nancy University Hospital
    Nancy, France

  • Borhane Slama, MD

    Hematology Department
    Avignon Hospital
    Avignon, France

  • Sabine Brechignac, MD

    Hematology Department
    Bobigny University Hospital
    Bobigny, France

  • Margaret Macro, MD

    Hematology Department
    Caen University Hospital
    Caen, France

  • Anne-Marie Stoppa, MD

    Hematology Department
    Institut Paoli Calmettes
    Marseille, France

  • Laurence Sanhes, MD

    Hematology Department
    Perpignan Hospital
    Perpignan, France

  • Frédérique Orsini-Piocelle, MD

    Hematology Department
    Annecy Hospital
    Annecy, France

  • Jean Fontan, MD

    Hematology Department
    Besançon University Hospital
    Besançon, France

  • Marie-Lorraine Chretien, MD, PhD

    Hematology Department
    Dijon University Hospital
    Dijon, France

  • Hélène Demarquette, MD

    Hematology Department
    Dunkerque Hospital
    Dunkerque, France

  • Mohamad Mohty, MD

    Hematology Department
    Saint-Antoine University Hospital
    Paris, France

  • Hervé Avet-Loiseau, MD, PhD

    Unit for Genomics in Myeloma, University Hospital IUC-Oncopole and Toulouse Cancer Research Center-Oncopole
    Toulouse University
    Inserm UMR1037
    Toulouse, France

  • Jill Corre, PharmD, PhD

    Unit for Genomics in Myeloma
    University Hospital IUC-Oncopole and Toulouse Cancer Research Center-Oncopole
    Toulouse University
    Inserm UMR1037
    Toulouse, France

CME Author

  • Laurie Barclay, MD

    Freelance writer and reviewer
    Medscape, LLC

    Disclosures

    Laurie Barclay, MD, has the following relevant financial relationships:
    Formerly owned stocks in: AbbVie Inc.

Editor

  • Andrew Roberts, MBBS, PhD

    Associate Editor, Blood

Compliance Reviewer

  • Leigh Schmidt, MSN, RN, CNE, CHCP

    Associate Director, Accreditation and Compliance, Medscape, LLC

    Disclosures

    Leigh Schmidt, MSN, RN, CNE, CHCP, has no relevant financial relationships.


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    For Physicians

  • Medscape, LLC designates this Journal-based CME activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™ . Physicians should claim only the credit commensurate with the extent of their participation in the activity.

    Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to 1.0 MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program. Participants will earn MOC points equivalent to the amount of CME credits claimed for the activity. It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting ABIM MOC credit.

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From Blood
CME / ABIM MOC

Biallelic Deletion of 1p32 Defines Ultra-High-Risk Myeloma, but Monoallelic del(1p32) Remains a Strong Prognostic Factor

Authors: Anaïs Schavgoulidze, PharmD; Alexis Talbot, MD; Aurore Perrot, MD, PhD; Titouan Cazaubiel, MD; Xavier Leleu, MD; Salomon Manier, MD, PhD; Laure Buisson, MsC; Sabrina Mahéo, MsC; Laura Do Souto Ferreira, MsC; Luka Pavageau, MsC; Cyrille Hulin, MD; Jean-Pierre Marolleau, MD; Laurent Voillat, MD; Karim Belhadj, MD; Marion Divoux, MD; Borhane Slama, MD; Sabine Brechignac, MD; Margaret Macro, MD; Anne-Marie Stoppa, MD; Laurence Sanhes, MD; Frédérique Orsini-Piocelle, MD; Jean Fontan, MD; Marie-Lorraine Chretien, MD, PhD; Hélène Demarquette, MD; Mohamad Mohty, MD; Hervé Avet-Loiseau, MD, PhD; Jill Corre, PharmD, PhDFaculty and Disclosures

CME / ABIM MOC Released: 3/16/2023

Valid for credit through: 3/16/2024, 11:59 PM EST

processing....

Abstract and Introduction

Abstract

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.

Introduction

Multiple myeloma (MM) is the second most frequent hematological malignancy in Western countries. The exceptional development in patient treatments has led to a significant improvement in overall survival (OS), both for patients who are eligible for transplant and for those who are not.[1] However, this improvement does not benefit patients at high risk who still represent an unmet medical need. It is unanimously recognized that cytogenetic abnormalities (CAs) displayed by malignant plasma cells (PCs) have a strong prognostic impact. Deletion 17p [del(17p)] is known to be the most unfavorable CA and affects ~8% of patients with newly diagnosed MM (NDMM). In 2015, del(17p) was integrated into the criteria of the revised version of the International Staging System (ISS) score, as well as 2 other CAs, translocations t(4;14) and t(14;16).[2]

CAs affecting chromosome 1, gain(1q) and del(1p32), were not included in these new criteria despite their relatively high frequencies, 35% and 11%, respectively, in patients with NDMM. However, previous or subsequent studies have distinctly demonstrated their negative effect on patients.[3-5] Moreover, Perrot et al have recently confirmed the significant prognostic impact of del(1p32) as being the second most adverse abnormality in myeloma, just after del(17p).[6]

This study aimed to update our data on the prognostic impact of del(1p32) in a large cohort of patients with NDMM, irrespectively of the therapeutic strategy used.