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

Jill Corre 1 Aurore Perrot 2 Denis Caillot 3 Karim Belhadj 4 Cyrille Hulin 5, 6 Xavier Leleu 7 Mohamad Mohty 8, 9 Thierry Facon 10 Laure Buisson 1 Laura Do Souto 1 Romain Lannes 1 Stephanie Dufrechou 1 Nais Prade 2 Frédérique Orsini-Piocelle 11 Laurent Voillat 12 Arnaud Jaccard 13 Lionel Karlin 14 Margaret Macro 15 Sabine Brechignac 16 Mamoun Dib 17 Laurence Sanhes 18 Jean Fontan 19 Lauriane Filliatre‐clement 20 Jean Pierre Marolleau 21 Stephane Minvielle 22 Philippe Moreau 23 Hervé Avet-Loiseau 1
1 IUCT Oncopole - UMR 1037 - Institut Universitaire du Cancer de Toulouse - Oncopole
2 CHU Toulouse [Toulouse]
3 CHU Dijon
4 Hôpital Henri Mondor
5 Hôpital Haut-Lévêque [CHU Bordeaux]
6 Institut François Magendie
7 Hôpital de la Milétrie
8 USPC - Université Sorbonne Paris Cité
9 CHU Saint-Antoine [AP-HP]
10 Service des Maladies du Sang [CHRU Lille]
11 Centre Hospitalier Annecy-Genevois [Saint-Julien-en-Genevois]
12 Centre Hospitalier Chalon-sur-Saône William Morey
13 CHU Limoges
14 CHLS - Centre Hospitalier Lyon Sud [CHU - HCL]
15 CHU Caen
16 Hôpital avicenne
17 CHU Angers - Centre Hospitalier Universitaire d'Angers
18 Centre Hospitalier Saint Jean de Perpignan
19 Hôpital Jean Minjoz
20 CHRU Nancy - Centre Hospitalier Régional Universitaire de Nancy
21 CHU Amiens-Picardie
22 CRCINA-ÉQUIPE 11 - Integrative Oncogenomics of Multiple Myeloma Pathogenesis and Progression
CRCINA - Centre de Recherche en Cancérologie et Immunologie Nantes-Angers
23 CHU Nantes - Centre hospitalier universitaire de Nantes
Abstract : 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.
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https://www.hal.inserm.fr/inserm-03010010
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Submitted on : Tuesday, November 17, 2020 - 3:15:32 PM
Last modification on : Friday, December 11, 2020 - 3:49:57 AM
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INSERM | UNIV-TLSE3 | HCL | CHLS | UNAM | CRCINA | UNIV-NANTES | UNIV-ANGERS | CNRS | UNIV-PARIS13 | COMUE-NORMANDIE | USPC | SORBONNE-UNIVERSITE | SU-TI

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Jill Corre, Aurore Perrot, Denis Caillot, Karim Belhadj, Cyrille Hulin, et al.. Del17p without TP53 mutation confers poor prognosis in intensively treated newly diagnosed multiple myeloma patients. Blood, American Society of Hematology, 2020, pp.blood.2020008346. ⟨10.1182/blood.2020008346⟩. ⟨inserm-03010010⟩

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