Blinatumomab consolidation for high-risk Ph− B-cell acute lymphoblastic leukemia: the GRAALL-2014/B-QUEST study
Abstract
Abstract Intensified chemotherapy regimens have improved outcomes in adults with Philadelphia chromosome–negative (Ph−) B-cell acute lymphoblastic leukemia (B-ALL), yet relapse remains a major cause of treatment failure and death. Blinatumomab is a T-cell engager that demonstrated marked activity in relapsed and measurable residual disease–positive (MRD+) B-ALL, as well as in frontline consolidation for MRD− patients. The phase 2 GRAALL-2014/B-QUEST substudy evaluated the integration of blinatumomab into consolidation and maintenance therapy for adults with high-risk (HR) B-ALL. Between 2015 and 2020, 489 adults aged 18 to 59 years with newly diagnosed Ph− B-ALL were enrolled, and among these 259 were classified as HR (presence of KMT2A-r, IKZF1 deletion, or end-of-induction MRD ≥ 10–4). A total of 94 patients with HR were enrolled in the QUEST study (2018-2020) and received up to 5, 28-day cycles of blinatumomab during consolidation and maintenance. In addition, 90 patients with HR who were treated before QUEST activation without blinatumomab served as controls in a post hoc analysis. Baseline characteristics were comparable between groups. Blinatumomab consolidation significantly improved MRD clearance, reduced relapse, and prolonged survival. At 5 years, cumulative incidence of relapse, disease-free survival (DFS), and overall survival were 23%, 68%, and 79% in the blinatumomab group compared with 49% (P = .001), 42% (P = .001), and 60% (P = .03) in controls. Patients eligible for allogeneic hematopoietic stem cell transplantation (alloHSCT) derived overall benefit. However, no clear additional DFS advantage was observed among those who ultimately underwent transplantation. These findings support the frontline integration of blinatumomab and warrant prospective evaluation of transplantation strategies in this setting. This trial was registered at www.clinicaltrials.gov as #NCT03709719.
Article Details
Authors (34)
Nicolas Boissel
Françoise Huguet
3Service d’Hématologie, Institut Universitaire du Cancer de Toulouse-Oncopole, Centre Hospitalier Universitaire de Toulouse, Toulouse, France
Thibaut Leguay
Mathilde Hunault
2Department of Hematology, Centre Hospitalier Universitaire d’Angers, INSERM, Centre National de la Recherche Scientifique, Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes Angers, Fédération Hospitalo-Universitaire Grand Ouest Against Leukemia, Université d’Angers, Université de Nantes, Angers, France
Rathana Kim
2Institut de Recherche Saint-Louis, Université Paris Cité, Paris, France
Yosr Hicheri
7Service d’Hématologie, Institut Paoli-Calmettes, Marseille, France
Marie Passet
2Institut de Recherche Saint-Louis, Université Paris Cité, Paris, France
Patrice Chevallier
Service d’Hématologie, Centre Hospitalier Universitaire (CHU) Hôtel Dieu, Nantes, France
Marie Balsat
9Service d’Hématologie, Hospices Civils de Lyon, Hôpital Lyon Sud, Pierre-Bénite, France
Cédric Pastoret
10Laboratoire d’Hématologie, Centre Hospitalier Universitaire de Rennes, Rennes, France
Éric Delabesse
26Laboratory of Hematology, Centre Hospitalier Universitaire de Toulouse, Toulouse, France
Sébastien Maury
12Service d’Hématologie Clinique, Hôpital Henri-Mondor, Assistance Publique-Hôpitaux de Paris, Paris, France
Anne Thiebaut-Bertrand
13Service d’Hématologie, Centre Hospitalier Universitaire Grenoble Alpes, Grenoble, France
Florence Van Obbergh
14Service d’Hématologie, Centre Hospitalier Universitaire HELORA–Hôpital de La Louvière/Jolimont, La Louvière, Belgium
Thomas Cluzeau
15Service d’Hématologie, Centre Hospitalier Universitaire de Nice, Nice, France
Martine Escoffre-Barbe
Service Hématologie, Hôpital Universitaire de Rennes, Rennes, France
Nicole Straetmans
17Service d’Hématologie, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium
Johanna Konopacki
18Service d’Hématologie, Hôpital d’Instruction des Armées Percy, Clamart, France
Amine Belhabri
19Service d’Hématologie, Centre Léon-Bérard, Lyon, France
Alban Villate
20Service d’Hématologie, Centre Hospitalier Régional Universitaire de Tours, Tours, France
Florence Pasquier
Ioana Vaida
22Service d’Hématologie, Hôpital René-Dubos (Nord-Ouest Val-d'Oise), Pontoise, France
Laurence Sanhes
22Department of Hematology, Centre Hospitalier de Perpignan, Perpignan, France
Sabine Blum
24Service d’Hématologie, Centre Hospitalier Universitaire Vaudois, Université de Lausanne, Lausanne, Switzerland
Magda Alexis
26Service d’Hématologie, Centre Hospitalier Régional d’Orléans, Orléans, France
Mathilde Lamarque
27Service d’Hématologie, Groupe Hospitalier Régional Mulhouse Sud-Alsace, Hôpital Émile-Muller, Mulhouse, France
Laure Farnault
28Service d’Hématologie, Assistance Publique-Hôpitaux de Marseille–Hôpital de la Conception, Marseille, France
Céline Berthon
29Service d’Hématologie, Centre Hospitalier Universitaire de Lille, Hôpital Claude-Huriez, Lille, France
Véronique Lhéritier
30Group for Research on Adult Acute Lymphoblastic Leukemia, Hôpital Lyon Sud, Pierre-Bénite, France
Norbert Ifrah
2Department of Hematology, Centre Hospitalier Universitaire d’Angers, INSERM, Centre National de la Recherche Scientifique, Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes Angers, Fédération Hospitalo-Universitaire Grand Ouest Against Leukemia, Université d’Angers, Université de Nantes, Angers, France
Carlos Graux
31Service d’Hématologie, Centre Hospitalier Universitaire, Université Catholique de Louvain Namur–Site Godinne, Yvoir, Belgium
Yves Chalandon
25Swiss Group for Clinical Cancer Research, Bern, Switzerland
Emmanuelle Clappier
2Institut de Recherche Saint-Louis, Université Paris Cité, Paris, France
Hervé Dombret