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Del17p without TP53 mutation confers poor prognosis in intensively treated newly diagnosed multiple myeloma patients

Authors :
Corre, Jill
Perrot, Aurore
Caillot, Denis
Belhadj, Karim
Hulin, Cyrille
Leleu, Xavier
Mohty, Mohamad
Facon, Thierry
Buisson, Laure
Do Souto, Laura
Lannes, Romain
Dufrechou, Stephanie
Prade, Nais
Orsini-Piocelle, Frédérique
Voillat, Laurent
Jaccard, Arnaud
Karlin, Lionel
Macro, Margaret
Brechignac, Sabine
Dib, Mamoun
Sanhes, Laurence
Fontan, Jean
Filliatre‐Clement, Lauriane
Marolleau, Jean Pierre
Minvielle, Stephane
Moreau, Philippe
Avet-Loiseau, Hervé
Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037)
Université Toulouse III - Paul Sabatier (UT3)
Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)
CHU Dijon
Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)
Hôpital Henri Mondor
Hôpital Haut-Lévêque [CHU Bordeaux]
CHU Bordeaux [Bordeaux]
Institut François Magendie
Hôpital de la Milétrie
Centre hospitalier universitaire de Poitiers (CHU Poitiers)
Université Sorbonne Paris Cité (USPC)
CHU Saint-Antoine [AP-HP]
Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Service des Maladies du Sang [CHU Lille] (SMS)
Hôpital Claude Huriez [Lille]
CHU Lille-CHU Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)
Centre Hospitalier Annecy-Genevois [Saint-Julien-en-Genevois]
Centre Hospitalier Chalon-sur-Saône William Morey
CHU Limoges
Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS)
Hospices Civils de Lyon (HCL)
CHU Caen
Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)
Hôpital Avicenne [AP-HP]
Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Centre Hospitalier Universitaire d'Angers (CHU Angers)
PRES Université Nantes Angers Le Mans (UNAM)
Centre Hospitalier Saint Jean de Perpignan
Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)
Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)
CHU Amiens-Picardie
Integrative Oncogenomics of Multiple Myeloma Pathogenesis and Progression (CRCINA-ÉQUIPE 11)
Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA)
Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)
Centre hospitalier universitaire de Nantes (CHU Nantes)
Bernardo, Elizabeth
Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)
CHU Toulouse [Toulouse]
Service des Maladies du Sang [CHRU Lille]
Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE)
Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE)
Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)
Source :
Blood, Blood, 2020, pp.blood.2020008346. ⟨10.1182/blood.2020008346⟩, Blood, American Society of Hematology, 2020, pp.blood.2020008346. ⟨10.1182/blood.2020008346⟩
Publication Year :
2020
Publisher :
HAL CCSD, 2020.

Abstract

International audience; Despite tremendous improvements in the outcome of patients with multiple myeloma (MM) in the past decade, high-risk patients have not benefited from the approval of novel drugs. The most important prognostic factor is the loss of parts of the short arm of chromosome 17, known as deletion 17p (del(17p)). A recent publication (on a small number of patients) suggested that these patients are at very high-risk only if del(17p) is associated with TP53 mutations, the so-called "double-hit" population. To validate this finding, we designed a much larger study on 121 patients presenting del(17p) in >55% of their plasma cells, and homogeneously treated by an intensive approach. For these 121 patients, we performed deep next generation sequencing targeted on TP53. The outcome was then compared to a large control population (2505 patients lacking del(17p)). Our results confirmed that the "double hit" situation is the worst (median survival = 36 months), but that del(17p) alone also confers a poor outcome compared with the control cohort (median survival = 52.8 months vs 152.2 months, respectively). In conclusion, our study clearly confirms the extremely poor outcome of patients displaying "double hit", but also that del(17p) alone is still a very high-risk feature, confirming its value as a prognostic indicator for poor outcome.

Details

Language :
English
ISSN :
00064971 and 15280020
Database :
OpenAIRE
Journal :
Blood, Blood, 2020, pp.blood.2020008346. ⟨10.1182/blood.2020008346⟩, Blood, American Society of Hematology, 2020, pp.blood.2020008346. ⟨10.1182/blood.2020008346⟩
Accession number :
edsair.dedup.wf.001..5c58d7f0e13a62865476fc897542290c
Full Text :
https://doi.org/10.1182/blood.2020008346⟩