Page 73 - Haematologica Vol. 107 - September 2022

ARTICLE - Acute Lymphoblastic Leukemia
High tumor burden before blinatumomab has a negative impact on the outcome of adult patients with B-cell precursor acute lymphoblastic leukemia. A real-world study by the GRAALL
Aurélie Cabannes-Hamy,1 Eolia Brissot,2 Thibaut Leguay,3 Françoise Huguet,4 Patrice Chevallier,5 Mathilde Hunault,6 Martine Escoffre-Barbe,7 Thomas Cluzeau,8 Marie Balsat,9 Stéphanie Nguyen,10 Florence Pasquier,11 Magda Alexis,12 Véronique Lhéritier,13 Cédric Pastoret,14 Eric Delabesse,15 Emmanuelle Clappier,16 Hervé Dombret17 and Nicolas Boissel18
1Hematology Department, Versailles Hospital, Le Chesnay; 2Sorbonne Université, AP-HP, Saint-Antoine Hospital, Hematology Department, UMRS 938, INSERM, Paris; 3Hematology Department, CHU de Bordeaux, Bordeaux; 4Hematology Department, CHU de Toulouse, Toulouse; 5Hematology Department, CHU de Nantes, Nantes; 6Hematology Department, CHU d'Angers, Angers; 7Hematology Department, CHU de Rennes, Rennes; 8Hematology Department, CHU de Nice, Nice; 9Hematology Department, Lyon Sud Hospital, Pierre Benite; 10Hematology Department, Pitié Salpêtrière Hospital, APHP, Paris; 11Hematology Department, Gustave Roussy, Villejuif; 12Hematology Department, Orléans Hospital, Orléans; 13GRAALL, CHU de Lyon, Lyon; 14Hematology Lab, CHU de Rennes, Rennes; 15Hematology Lab, CHU de Toulouse, Toulouse; 16Hematology Lab, Saint-Louis Hospital, APHP, Paris; 17Adult Hematology Department, Saint-Louis Hospital, APHP, URP3518, Institut de Recherche Saint-Louis, Université de Paris, Paris and 18Hematology Adolescent and Young Adult Unit, Saint-Louis Hospital, APHP, URP3518, Institut de Recherche Saint-Louis, Université de Paris, Paris, France
Abstract
Blinatumomab is a bispecific T-cell engager approved for B-cell precursor acute lymphoblastic leukemia (B-ALL) with persistent minimal residual disease (MRD) or in relapse. The prognostic impact of tumor load has been suggested before other immunotherapies but remains poorly explored before blinatumomab. We retrospectively analyzed the outcome of 73 patients who received blinatumomab either in first complete remission (CR) with MRD (n=35) or at relapse (n=38). Among MRD patients, 91% had MRD >0.01% before blinatumomab, and 89% achieved complete MRD response after blinatumomab. High pre-blinatumomab MRD levels were associated with shorter relapse-free survival (P=0.049) and overall survival (OS) (P=0.011). At 3 years, OS was 33%, 58% and 86% for pre-blinatumomab MRD >1%, between MRD 0.1- 1% and <0.1% respectively. Among relapsed patients, 23 received blinatumomab with overt relapse and 15 were in complete response (CR) after bridging chemotherapy. At 3 years, overall CR rate was 68% and complete MRD response rate was 84%. Patients who directly received blinatumomab had shorter relapse-free survival (P=0.033) and OS (P=0.003) than patients bridged to blinatumomab. Three-year OS was 66% in the latter group compared to 16% in the former group. Our observations suggest that pre-blinatumomab tumor burden should help to design more tailored strategies including tumor load reduction in relapsed patients.
Introduction
The outcome of adult patients with B-cell precursor acute lymphoblastic leukemia (BCP-ALL) has been dramatically improved in the last decades by the use of pediatric-in- spired chemotherapy regimen,1–3 the risk stratification based on minimal residual disease (MRD),4,5 and the intro- duction of tyrosine kinase inhibitor (ITK) in Philadelphia positive (Ph+) BCP-ALL.6,7 More than 90% of patients
below the age of 60 years achieve complete remission (CR) after induction with 5-year overall survival (OS) of about 60%. Early evaluation of MRD has been shown to be the most powerful prognostic factor associated with the risk of relapse.4 A high MRD level after induction or during consolidation reflects a poor response to chemo- therapy, and identifies patients that benefit from alloge- neic hematopoietic stem cell transplantation (HSCT) in first CR.5 Despite a global improvement in survival, about
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Correspondence: N. Boissel nicolas.boissel@aphp.fr
Received: Accepted: Prepublished:
September 27, 2021. February 28, 2022. March 10, 2022.
https://doi.org/10.3324/haematol.2021.280078
©2022 Ferrata Storti Foundation Published under a CC BY-NC license