PURPOSE: The use of inotuzumab ozogamicin (InO), a conjugated anti-CD22 monoclonal antibody, is becoming a promising frontline treatment for older patients with ALL. PATIENTS AND METHODS: EWALL-INO is an open-label prospective multicenter phase II trial (ClinicalTrials.gov identifier: NCT03249870). Patients age 55 years and older with newly diagnosed CD22+ Philadelphia chromosome-negative (Ph-) B-cell precursor (BCP) ALL were eligible. After a prephase, a first induction consisting of vincristine, dexamethasone, and three injections of InO (0.8 mg/m2 day 1, 0.5 mg/m2 day 8/day 15) was followed by a second induction combining cyclophosphamide, dexamethasone, and two injections of InO (0.5 mg/m2 day 1/day 8). Responders received up to six cycles of chemotherapy consolidation and 18-month chemotherapy maintenance. Allotransplant was allowed after three consolidations. The primary end point was 1-year overall survival (OS). RESULTS: Between December 2017 and March 2022, 131 patients (median age 68 years) were included. Three patients died during induction 1 (n = 130), two from multiple organ failure and one from hemorrhage, and none during induction 2 (n = 120). After induction 2, 90% of the patients achieved complete remission (CR) or CR with incomplete platelet recovery (CRp) and 80% had measurable residual disease (MRD2) <10-4. Among responders (n = 119), 47 relapsed and 14 died in CR/CRp. One-year OS, relapse-free survival (RFS), and cumulative incidence of relapse (CIR) rates were 73.2%, 66%, and 25%, respectively. High-risk cytogenetics and lower CD22 expression (<70%) were associated with worse OS, while both high-risk cytogenetics and MRD2 ≥10-4 were associated with lower RFS and higher CIR. The 10 allotransplanted patients had very favorable outcomes (90% 2-year OS/RFS and no relapse). Only one nonfatal sinusoidal obstructive syndrome was documented during the study. CONCLUSION: Our results support InO's use in first-line regimens for older patients with CD22+ Ph- BCP-ALL.

CRCI2NA INSERM UMR 1307 and CNRS UMR 6075 IRS_UN University of Nantes Nantes France

Department of Population Health Sciences School of Life Course and Population Sciences King's College London London United Kingdom

Division of Hematology Centre Hospitalier de Versailles Université Versailles Paris Saclay Le Chesnay France

Hematology Department Centre Henri Becquerel Rouen France

Hematology Department Centre Lyon Bérard Lyon France

Hematology Department CHR d'Orleans Orleans France

Hematology Department CHR de la Côte Basque Bayonne France

Hematology Department CHR Métropole Savoie Chambéry France

Hematology Department CHU Amiens Sud Amiens France

Hematology Department CHU d'Angers Angers France

Hematology Department CHU de Caen Caen France

Hematology Department CHU de Clermont Ferrand Clermont Ferrand France

Hematology Department CHU de Dijon Dijon France

Hematology Department CHU de Limoges Limoges France

Hematology Department CHU de Nancy Nancy France

Hematology Department CHU de Nîmes Nîmes France

Hematology Department CHU de Reims Reims France

Hematology Department CHU de St Etienne Saint Priest en Jarez France

Hematology Department CHU Hôpital Haut Lévèque Pessac France

Hematology Department CHU Jean Minjoz Besançon France

Hematology Department Fakulni Nemocnice Brno Brno Czech Republic

Hematology Department Helsinki University Hospital Helsinki Finland

Hematology Department Hôpital Archet CHU Nice Nice France

Hematology Department Hôpital Avicenne APHP Paris France

Hematology Department Hôpital Pontchaillou CHU Rennes France

Hematology Department Hôpital St Eloi CHU Montpellier France

Hematology Department Hôpital St Louis APHP Paris France

Hematology Department Hôpital Victor Provo Roubaix France

Hematology Department Hospices Civils de Lyon Hôpital Lyon Sud Pierre Bénite France

Hematology Department Institut de Cancérologie Strasbourg Europe Strasbourg France

Hematology Department Institut Paoli Calmettes Marseille France

Hematology Department Institut Universitaire du Cancer de Toulouse Oncopole Centre Hospitalier Universitaire Toulouse France

Hematology Department Nantes University Hospital Nantes France

Hematology Department Unité Adolescent et Jeunes Adultes Préservation de la Fertilité Hôpital St Louis APHP Paris and EA 3518 Institut Universitaire d'Hématologie Université Paris 7 Paris France

Institut de Recherche Saint Louis Centres de Recherches Paris and Département de l'UFR de Médecine de l'Université Paris Diderot Paris 7 Paris France

Institute of Hematology and Blood Transfusion and Charles University 1st Faculty of Medicine Prague Czech Republic

Service d'Hématologie Biologique Hôpital Saint Louis Université Paris Cité INSERM CNRS U944 UMR7212 Paris France

Sorbonne University Hematology Department Saint Antoine Hospital INSERM UMR 938 Paris France

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ClinicalTrials.gov
NCT03249870