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211 Blinatumomab during Consolidation in High-Risk Philadelphia Chromosome (Ph)-Negative B-Cell Precursor (BCP) Acute Lymphoblastic Leukemia (ALL) Adult Patients: A Two-Cohort Comparison within the Graall-2014/B StudyClinically Relevant Abstract

Program: Oral and Poster Abstracts
Type: Oral
Session: 614. Acute Lymphoblastic Leukemias: Therapies, Excluding Transplantation and Cellular Immunotherapies: Clinical Trials
Hematology Disease Topics & Pathways:
Research, clinical trials, Lymphoid Leukemias, ALL, Biological therapies, Bispecific Antibody Therapy, Clinical Research, Diseases, Therapies, Lymphoid Malignancies, Minimal Residual Disease
Saturday, December 10, 2022: 2:00 PM

Nicolas Boissel, MD, PhD1,2, Francoise Huguet, MD3*, Thibaut Leguay, MD4*, Mathilde Hunault, MD; PhD5*, Rathana KIM, PharmD6*, Yosr Hicheri, MD7*, Patrice Chevallier, MD8, Marie Balsat9*, Sébastien Maury10*, Anne Thiebaut-Bertrand11*, Florence Van Obbergh12*, Thomas Cluzeau, MD, PhD13, Martine Escoffre-Barbe, MD14*, Nicole Straetmans, MD, PhD15, Johanna Konopacki16*, Amine Belhabri17*, Alban Villate, MD18*, Florence Pasquier, MD, PhD19*, Ioana Vaida, MD20*, Laurence Sanhes, MD21*, Magda Alexis, MD22*, Cedric Pastoret, MD, PhD23*, Mathlide Lamarque, MD24*, Laure Farnault, MD25*, Nathalie Grardel, MD26*, Celine Berthon, MD, PhD27*, Eric Delabesse, MD, PhD28*, Veronique Lheritier29*, Norbert Ifrah, MD PhD30, Carlos Graux31*, Yves Chalandon, MD32, Emmanuelle Clappier, PharmD, PhD33* and Herve Dombret, MD PhD34,35

1St-Louis Hospital, APHP, Adolescent and Young Adult Hematology Department, Paris, France
2URP-3518, Saint-Louis Research Insitute, Université Paris Cité, Paris, France
3Department of Hematology, Institut Universitaire du Cancer-Oncopole CHU de Toulouse, Toulouse, France
4Hematology Clinic, Bordeaux University Hospital, Pessac, France
5Clinical Hematology, CHU d'Angers, Angers, France
6Hematology laboratory, Assistance Publique Des Hopitaux De Paris (AP-HP) - Universite Paris Descartes -, Paris, Ile-de-France, France
7Departement d'Hematologie, Institut Paoli-Calmettes, MARSEILLE, France
8Hematology Department, Nantes University Hospital, Nantes, France
9Service Hematologie, Centre Hospitalier Lyon Sud, Lyon, France
10Service d’Hématologie clinique, Hôpitaux universitaires Henri-Mondor (AP-HP), Créteil, FRA
11CHU de Grenoble, Grenoble, France
12CH Jolimont, Hematology Department, La Louviere, BEL
13Département d'Hématologie Clinique, Université Côte d'Azur, CHU Nice, Nice, Provence Alpes Cote d'Azur, France
14Hôpital de Pontchaillou, Centre Hospitalier Universitaire de Rennes, Rennes, France
15Department of Hematology, Cliniques Universitaires Saint-Luc,, Woluwe Saint Lambert, BEL
17Centre Leon Berard, Departement Oncologie Medicale, Lyon, France
18Service d'hématologie et thérapie cellulaire, Hôpital Bretonneau, CHRU de Tours, Tours, France
19Gustave Roussy, Département clinique d'hématologie, INSERM UMR1170, Villejuif, FRA
20Hematology Department, Pontoise Hospital, Pontoise, France
21Department of Hematology, CH de Perpignan, Perpignan, France
22CHR d'Orléans, Orleans, FRA
23INSERM U1236 /Hematology Laboratory, University Hospital of Rennes, RENNES, FRA
24Service d'Hématologie, Centre Hospitalier de Mulhouse, Mulhouse, FRA
25Service d'hématologie clinique et de thérapie cellulaire, Assistance Publique des Hôpitaux de Marseille, Centre Hospitalier Universitaire La Conception, Marseille, France
26Laboratory of Hematology, Centre Hospitalier Universitaire Lille, Lille, France
27Hematology Department, Lille University Hospital, Lille, France
28Hematology Laboratory, Institut Universitaire du Cancer Toulouse Oncopole, Toulouse, France
29Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL), Centre Hospitalier Lyon Sud, Lyon, France
30Clinical Hematology, Angers University Hospital, Angers, France
31Université Catholique de Louvain, CHU UCL Namur (Godinne), Yvoir, Belgium
32Geneva University Hospitals, Geneva, Switzerland
33Hematology Laboratory and INSERM U944, Saint-Louis Hospital, AP-HP, Paris, France
34URP-3518, Institut de Recherche Saint-Louis, Université Paris Cité, Paris, France
35Hopital Saint-Louis, Assistance Publique - Hopitaux De Paris (AP-HP), Paris, FRA


ALL with unfavorable biology and/or high minimal residual disease (MRD) levels are at high-risk of disease recurrence. Based on the GRAALL-2005/B analysis (Beldjord K et al, Blood 2014), Ph-negative BCP-ALL patients enrolled in the GRAALL-2014/B trial were classified at high-risk (HR) if presenting KMT2A-rearrangement (KMT2A-r), IKZF1 intragenic deletion (IKZF1del), and/or IG/TR post-induction MRD1 ≥ 10-4 (including the need of a salvage course to reach a first complete remission [CR]). In the nested phase 2 QUEST sub-study (initiated by amendment during the GRAALL-2014/B course), those patients were offered to receive blinatumomab during consolidation and maintenance or as bridge to allogeneic hematopoietic stem cell transplantation (HSCT). The aim of the present report is to compare their outcome to that of similar patients treated in the same GRAALL-2014/B trial but without frontline blinatumomab.

Patients and methods

Between December 2015 and December 2020, the GRAALL-2014/B trial included 489 patients with Ph-negative BCP-ALL. Among these patients, 266 presented with HR features as defined above. The QUEST study amendment occurred in October 2018. QUEST eligibility was HR patients with no CNS involvement at baseline who started consolidation 2 at week 12 in continuous CR. Blinatumomab was given as bridge to transplant for patients with MRD1 ≥ 10-3 and/or with post-consolidation 1 MRD2 ≥ 10-4 with an available matched sibling or unrelated donor (10/10 or 9/10). Other patients received up to 5 cycles of blinatumomab during consolidation and maintenance phases. A total of 95 patients, including 94 evaluable patients, were included in QUEST between October 2018 and December 2020. A total of 104 control patients treated in the GRAALL-2014/B met the QUEST eligibility criteria but were not included in this sub-study, either before QUEST activation (n=92), or during accrual (n=6), or after accrual completion (n=6). The QUEST cohort (n=93) was compared to the control cohort (n=104) for disease-free survival (DFS, primary endpoint), MRD evolution, relapse, and overall survival (OS).


Patients from both QUEST and control cohorts had similar baseline characteristics (Table 1). Notably, there was no differences in terms of HR features, including KMT2A-r and IKZF1del rates. As per protocol, all patients were in CR with no difference in terms of second induction requirement to reach CR. Both cohorts had comparable MRD1 and MRD2 levels. Patients included in the QUEST study reached lower MRD3 (post-consolidation 2) levels. Among patients with MRD2 ≥ 10-4, undetectable MRD was achieved at MRD3 in 23/41 (56%) after blinatumomab versus 4/29 (14%) after chemotherapy alone (p<0.001). The rate of HSCT in first CR did not statistically differ among both cohorts. QUEST patients, who received blinatumomab, had a lower cumulative incidence of relapse (CIR; SHR 0.48, 95% CI [0.28-0.83]; p=0.009) and a prolonged disease-free survival (DFS; HR 0.59, 95% CI [ 0.37-0.96]; p=0.03), with no difference in terms of overall survival (OS; HR 0.67, 95% CI [0.36-1.25], p=0.21) (Table 1, Figure 1). These differences were also observed after censoring patients at the time of allo-HSCT, or when excluding from the control group patients not enrolled in the QUEST study during accrual period.


With the limitations of a non-controlled study but in patients all enrolled in the same prospective GRAALL-2014/B trial, this observation suggests that blinatumomab in consolidation benefits to HR Ph-negative BCP-ALL patients by markedly reducing the risk of relapse. Phase 3 studies are ongoing or about to start to confirm this observation.

Disclosures: Boissel: GILEAD: Honoraria; AMGEN: Honoraria; ARIAD/INCYTE: Honoraria; ASTELLAS: Honoraria; NOVARTIS: Honoraria; SERVIER: Honoraria. Huguet: novartis: Honoraria; incyte: Honoraria; bms: Honoraria; amgen: Honoraria; pfizer: Honoraria; jazz pharma: Honoraria. Leguay: Amgen: Consultancy; Servier: Consultancy. Hunault: clinigen: Honoraria, Membership on an entity's Board of Directors or advisory committees; jazz pharmaceutical: Honoraria, Membership on an entity's Board of Directors or advisory committees; incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees; servier: Honoraria, Membership on an entity's Board of Directors or advisory committees; abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees. Chevallier: Abbvie: Honoraria; Incyte: Research Funding; Takeda: Honoraria; Pfizer: Research Funding; Jazz Pharmaceuticals: Honoraria. Cluzeau: BMS/Celgene, Novartis, Jazz: Consultancy, Speakers Bureau; AbbVie, Astellas, Servier: Speakers Bureau. Chalandon: Jazz: Other: consulting fees+ travel support; Roche: Other: consulting fees + travel support; Gilead: Other: consulting fees + travel support; Pfizer: Other: consulting fees; BMS: Other: consulting fees; Astra-Zeneca: Other: consulting fees + travel support; Amgen: Other: consulting fees + travel support; Incyte: Other: consulting fees + travel support; Novartis: Other: consulting fees; MSD: Other: consulting fees+ travel support; Abbvie: Other: consulting fees + travel support; Servier: Other: consulting fees; Janssen: Other: Travel support.

OffLabel Disclosure: Blinatumomab in consolidation for frontline high-risk Philadelphia-negative ALL

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