Inotuzumab Ozogamicin and Low-Intensity Chemotherapy in Older Patients With Newly Diagnosed CD22 <sup>+</sup> Philadelphia Chromosome–Negative B-Cell Precursor Acute Lymphoblastic Leukemia
Patrice Chevallier, Thibaut Leguay, Marc Delord, Cyril Šálek, Rathana Kim, Françoise Huguet, Yosr Hicheri, Ulla Wartiovaara‐Kautto, Emmanuel Raffoux, Thomas Cluzeau, Marie Balsat, Gabrielle Roth-Guépin, Emmanuelle Tavernier, Stéphane Leprêtre, Karin Bilger, Hugo Bergugnat, Ana Berceanu, Magda Alexis, Michael Doubek, Éolia Brissot, Mathilde Hunault, Delphine Lebon, Pascal Turlure, Sylvain Chantepie, Amine Belhabri, Stefan Wickenhauser, Jean Bastié, Victoria Cacheux, Chantal Himberlin, Anne Banos, Claude Gardin, Sarah Bonnet, Isabelle Plantier, Gian Matteo Pica, Martine Escoffre‐Barbe, Nicolas Boissel, Hervé Dombret, Emmanuelle Clappier, Philippe Rousselot, Delphine Lebon, Amandine Charbonnier, Déborah Assouan, Amandine Hubert, Marine Quint, Fulvia Guenbem Kossi, Elodie Deruche, Mathilde Hunault, Céline Marie, Anne Banos, Jean‐Baptiste Robin, Julie Gay, C. Capdupuy, Sévérine Labarrere, Edith Vincent, Marion Simonet‐Boissard, Ana Berceanu, Fabrice Larosa, Yohan Desbrosses, Guillaume Boiteux, Vinciane Dufour, Elise Tissot, Thorsten Braun, P Gardin, Valérie Vidal, Geoffrey Edouart, Sylvain Chantepie, Jean‐Pierre Vilque, Hyacinthe Johnson Ansah, Angélique Lebouvier, Marie Charlotte Zapalovicz, Léa Renault, Pica Gian Matteo, Alix Courouau, Fabienne Prieur, Charlene Dupre, Victoria Cacheux, Benoît De Renzis, Carine Chaleteix, Amandine Fayard, Gwendoline Roy, Jean Bastié, Denis Caillot, Laetitia Devaux, Patrice Chevallier, Amandine Lebourgeois, Antoine Bonnet, Pierre Péterlin, Anne Lok, Thierry Guilllaume, Alexis Morice Fontaine, Pascal Turlure, Mohamed Touati, Céline Kennel, Natalya Dmytruck, Julie Abraham, Arnaud Jaccard, Liliane Réménieras, Stéphane Girault, Marie Pierre Gourin, Amélie Penot
Abstract
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/m 2 day 1, 0.5 mg/m 2 day 8/day 15) was followed by a second induction combining cyclophosphamide, dexamethasone, and two injections of InO (0.5 mg/m 2 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.