Pomalidomide plus low-dose dexamethasone in multiple myeloma with deletion 17p and/or translocation (4;14): IFM 2010-02 trial results.

Xavier Leleu , Lionel Karlin (1) , Margaret Macro , Cyrille Hulin , Laurent Garderet (2) , Murielle Roussel (3) , Bertrand Arnulf (4) , Brigitte Pegourie , Brigitte Kolb , Anne Marie Stoppa , Sabine Brechiniac , Gerald Marit (5) , Beatrice Thielemans , Brigitte Onraed , Claire Mathiot (6) , Anne Banos , Laurence Lacotte , Mourad Tiab , Mamoun Dib , Jean-Gabriel Fuzibet , Marie Odile Petillon , Philippe Rodon , Marc Wetterwald , Bruno Royer (7, 8) , Laurence Legros (9) , Lotfi Benboubker , Olivier Decaux (10) , Martine Escoffre-Barbe (11) , Denis Caillot (12) , Jean Paul Fermand , Philippe Moreau , Michel Attal (13) , Herve Avet-Loiseau (14) , Thierry Facon (15, 16)

1 Service d'immunologie
2 UMR_S567 / UMR 8104 - Institut Cochin
3 CHU Pontchaillou [Rennes]
4 Service d'hématologie biologique
5 Service des maladies du sang
6 Laboratoire d'Hématologie biologique
7 Service d'hématologie
8 RIGHT - Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098)
9 Foie, métabolismes et cancer
10 IGDR - Institut de Génétique et Développement de Rennes
11 Service d'hématologie clinique
12 CHU Dijon
13 Service Hématologie - IUCT-Oncopole [CHU Toulouse]
14 Service d'hématologie clinique
15 IMRB - Institut Mondor de Recherche Biomédicale
16 Hôpital Claude Huriez [Lille]

The combination of pomalidomide and low-dose dexamethasone (Pom-Dex) can be safely administered to patients with end-stage relapsed/refractory multiple myeloma (RRMM). However, we observed a shorter median progression-free survival (PFS) and overall survival (OS) in these patients when characterized with adverse cytogenetics (deletion 17p and translocation [4;14]) in the Intergroupe Francophone Myélome (IFM) 2009-02 trial. We then sought to determine whether MM with adverse cytogenetics would benefit more from Pom-Dex if exposed earlier in the multicenter IFM 2010-02 trial. The intention-to-treat population included 50 patients, with a median age of 63 years (38% were ≥65 years). Interestingly, there was a striking difference in time to progression (TTP), duration of response, and overall response rate (ORR) according to the presence of del(17p) compared with t(4;14) (TTP, 7.3 vs 2.8 months; duration of response, 8.3 vs 2.4 months; and ORR, 32% vs 15%). OS was prolonged after Pom-Dex, particularly in t(4;14), given the short TTP, suggesting that patients were rescued at relapse with further lines of therapy. Pom-Dex, a doublet immunomodulatory drug-based regimen, is active and well tolerated in adverse cytogenetic patients with early RRMM, particularly in those with del(17p), who are characterized by a high and rapid development of a refractoriness state and known for their poor prognosis. Future studies will determine the underlying mechanisms of Pom-Dex activity in del(17p). This trial is registered at www.clinicaltrials.gov as #NCT01745640.

Domains: Life Sciences [q-bio]

Xavier Leleu, Lionel Karlin, Margaret Macro, Cyrille Hulin, Laurent Garderet, et al.. Pomalidomide plus low-dose dexamethasone in multiple myeloma with deletion 17p and/or translocation (4;14): IFM 2010-02 trial results.. Blood, 2015, 125 (9), pp.1411-7. ⟨10.1182/blood-2014-11-612069⟩. ⟨hal-01141134⟩