Ruxolitinib before allogeneic hematopoietic transplantation in patients with myelofibrosis on behalf sfgm-tc and fim groups
Marie Robin
(1)
,
Raphael Porcher
(2)
,
Corentin Orvain
(3)
,
Jacques-Olivier Bay
(4)
,
Fiorenza Barraco
(5)
,
Anne Huynh
(6)
,
Amandine Charbonnier
(7)
,
Edouard Forcade
(8)
,
Sylvain P. Chantepie
(9)
,
Claude-Éric Bulabois
(10)
,
Ibrahim Yakoub-Agha
(11)
,
Marie Detrait
(12)
,
David Michonneau
(13)
,
Pascal Turlure
(14)
,
Nicole Raus
(5)
,
Francoise Boyer
(3)
,
Felipe Suarez
(15)
,
Laure Vincent
(16)
,
Stéphanie Nguyen-Quoc
(17)
,
Jerome Cornillon
(18)
,
Alban Villate
(19)
,
Brigitte Dupriez
(20)
,
Bruno Cassinat
(1)
,
Valerie Rolland
(21)
,
Marie Helene Schlageter
(1)
,
Gerard Socie
(13)
,
Jean-Jacques Kiladjian
(1)
1
AP-HP -
Hopital Saint-Louis [AP-HP]
2 CRESS (U1153 / UMR_A 1125) - Centre for Research in Epidemiology and Statistics | Centre de Recherche Épidémiologie et Statistiques
3 CHU Angers - Centre Hospitalier Universitaire d'Angers
4 Service d’Hématologie Biologique [CHU Clermont-Ferrand]
5 CHLS - Centre Hospitalier Lyon Sud [CHU - HCL]
6 IUCT Oncopole - UMR 1037 - Institut Universitaire du Cancer de Toulouse - Oncopole
7 CHU Amiens-Picardie
8 Hôpital Haut-Lévêque [CHU Bordeaux]
9 Laboratoire d'Hématologie Biologique [CHU Caen]
10 CHUGA - Centre Hospitalier Universitaire [CHU Grenoble]
11 INFINITE - Institute for Translational Research in Inflammation - U 1286
12 UL - Université de Lorraine
13 UPCité - Université Paris Cité
14 Service d'Hématologie clinique et thérapie cellulaire [CHU Limoges]
15 Imagine - U1163 - Imagine - Institut des maladies génétiques (IHU)
16 CHU Montpellier
17 CHU Pitié-Salpêtrière [AP-HP]
18 ICHUSE - Institut de Cancérologie et d'Hématologie Universitaire de Saint-Étienne [CHU Saint-Etienne]
19 Hôpital Bretonneau
20 Centre Hospitalier de Lens
21 IBMM - Institut des Biomolécules Max Mousseron [Pôle Chimie Balard]
2 CRESS (U1153 / UMR_A 1125) - Centre for Research in Epidemiology and Statistics | Centre de Recherche Épidémiologie et Statistiques
3 CHU Angers - Centre Hospitalier Universitaire d'Angers
4 Service d’Hématologie Biologique [CHU Clermont-Ferrand]
5 CHLS - Centre Hospitalier Lyon Sud [CHU - HCL]
6 IUCT Oncopole - UMR 1037 - Institut Universitaire du Cancer de Toulouse - Oncopole
7 CHU Amiens-Picardie
8 Hôpital Haut-Lévêque [CHU Bordeaux]
9 Laboratoire d'Hématologie Biologique [CHU Caen]
10 CHUGA - Centre Hospitalier Universitaire [CHU Grenoble]
11 INFINITE - Institute for Translational Research in Inflammation - U 1286
12 UL - Université de Lorraine
13 UPCité - Université Paris Cité
14 Service d'Hématologie clinique et thérapie cellulaire [CHU Limoges]
15 Imagine - U1163 - Imagine - Institut des maladies génétiques (IHU)
16 CHU Montpellier
17 CHU Pitié-Salpêtrière [AP-HP]
18 ICHUSE - Institut de Cancérologie et d'Hématologie Universitaire de Saint-Étienne [CHU Saint-Etienne]
19 Hôpital Bretonneau
20 Centre Hospitalier de Lens
21 IBMM - Institut des Biomolécules Max Mousseron [Pôle Chimie Balard]
Résumé
This multicenter prospective phase 2 trial analyzed disease-free survival (DFS) in myelofibrosis patients receiving ruxolitinib for 6 months before transplantation. Seventy-six patients were recruited. Age-adjusted dynamic international prognostic scoring system was intermediate-1, intermediate-2, and high in 27 (36%), 31 (41%), and 18 (24%) patients. All patients received ruxolitinib from inclusion to conditioning regimen (fludarabine-melphalan) or to progression. A donor was found in 64 patients: 18 HLA-matched sibling donor (MSD), 32 HLA-matched unrelated (UD10/10), and 14 HLA mismatched unrelated donor (UD9/10. Among 64 patients with a donor, 20 (31%) achieved a partial response before transplantation and 59 (92%) could be transplanted after ruxolitinib therapy (18/18 MSD, 30/21 UD10/10, 11/34 UD9/10), of whom 19 (32%) were splenectomized. Overall survival from inclusion was 68% at 12 months. One-year DFS after transplantation was 55%: 83%, 40%, and 34% after MSD, UD10/10 or UD9/10, respectively. Cumulative incidence of grade 2-4 acute graft-versus-host disease (GVHD) was 66% and non-relapse-mortality was 42% at 12 months. Short course of ruxolitinib before transplantation is followed by a high rate of transplantation. With the platform used in this protocol, outcome was much better in patients transplanted with HLA-matched sibling donor as compared to unrelated donor.