Inotuzumab Ozogamicin and Low-Intensity Chemotherapy in Older Patients With Newly Diagnosed CD22
+
Philadelphia Chromosome–Negative B-Cell Precursor Acute Lymphoblastic Leukemia
Authors: Chevallier Patrice , Leguay Thibaut , Delord Marc , Salek Cyril , Kim Rathana , Huguet Françoise , Hicheri Yosr , Wartiovaara-Kautto Ulla , Raffoux Emmanuel , Cluzeau Thomas , Balsat Marie , Roth-Guepin Gabrielle , Tavernier Emmanuelle , Lepretre Stephane , Bilger Karin , Bergugnat Hugo , Berceanu Ana , Alexis Magda , Doubek Michael , Brissot Eolia , Hunault-Berger Mathilde , Lebon Delphine , Turlure Pascal , Chantepie Sylvain , Belhabri Amine , Wickenhauser Stefan , Bastie Jean-Noel , Cacheux Victoria , Himberlin Chantal , Banos Anne , Gardin Claude , Bonnet Sarah , Plantier Isabelle , Pica Gian Matteo , Escoffre-Barbe Martine , Boissel Nicolas , Dombret Herve , Clappier Emmanuelle , Rousselot Philippe ,   on behalf of The Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL) and the European Working Group for Adult Acute Lymphoblastic Leukemia (EWALL), Lebon Delphine , Charbonnier Amandine , Assouan Deborah , Hubert Amandine , Quint Marine , Kossi Fulvia Guenbem , Deruche Elodie , Hunault Mathilde , Marie Céline , Banos Anne , Robin Jean-Baptiste , Gay Julie , Capdupuy Claudie , Labarrere Sévérine , Vincent Edith , Simonet-Boissard Marion , BeRceanu Ana , Larosa Fabrice , Desbrosses Yohan , Boiteux Guillaume , Dufour Vinciane , Tissot Elise , Braun Thorsten , Gardin Pr Claude , Vidal Valérie , Edouart Geoffrey , Chantepie Sylvain , Vilque Jean-Pierre , Johnson Ansah Hyacinthe , Lebouvier Angélique , Zapalovicz Marie Charlotte , Renault Léa , Gian Matteo Pica , Courouau Alix , Prieur Fabienne , Dupre Charlene , Cacheux Victoria , De Renzis Benoit , Chaleteix Carine , Fayard Amandine , Roy Gwendoline , Bastie Jean-Noël , Caillot Denis , Devaux Laetitia , Chevallier Patrice , Lebourgeois Amandine , Bonnet Antoine , Peterlin Pierre , Lok Anne , Guilllaume Thierry , Fontaine Alexis Morice , Turlure Pascal , Touati Mohamed , Kennel Céline , Dmytruck Natalya , Abraham Julie , Jaccard Arnaud , Remenieras Liliane , Girault Stéphane , Gourin Marie Pierre , Penot Amélie , Moreau Stéphane , Philipon Céline , Roche Delphine , Belhabri Amine , Gilis Lila , Virelizier Nicolas , Michalet Anne-Sophie , Monfray Jérémy , Balsat Marie , Thomas Xavier , Praire Aline , Guepin Gabrielle Roth , Bonmati Caroline , Moulin Charline , Jacquet Caroline , Carpodomi Anne , Bouillet Hélène , Carpentier Odile , Montero Mélanie , Pires Aude , Gastaud Lauris , Gama Anastasia , Coelle Céline , Karmout Sonia , Cluzeau Thomas , Loschi Michael , Lechardeur Jessica , Chokri Hatroubi , Broussot Loic , Wickenhauser Stefan , Waulthier Agathe , Jourdan Eric , Scherman Elodie , Umuhire Diane , Damiano Maria Alessandra , Hicheri Yors , Saillard Colombe , D'Incan Evelyne , Hospital Marie-Anne , L'Attention Jean Laurent , Rabah Mme Nassima , Cesari Laura Castillo , Gehlkopf Eve , Vincent Laure , Navarro Robert , Quittet Philippe , Fegueux Nathalie , Ceballos Patrice , Marin Fanny Baguet , Sabadash Véra , Alexis Magda , Ochmann Marlène , Laboure Nina Akakelyan , Bembrahmi Omar , Michel Olivier , Ouahrawi Brahim , Brissot Eolia , Legrand Olivier , Vekhoff Anne , Isnard Françoise , Sa Sara E. , Dombret Hervé , Raffoux Emmanuel , Lenguine Etienne , Rabian Florence , Lebras Karine Celli , Fauvaux Catherine , Leguay Thibaut , Gros François-Xavier , Debus  , Cazaubiel Titouan , Melot Cyril , Dematteis Valentin , Messina Antonella , Himberlin Chantal , Le Quoc-Hung , Maggi Lucia , Barre Martine Escoffre , Moignet Aline , De Guibert Sophie , Bernard Marc , Decaux Olivier , de la Chapelle Thierry Lamy , Nimubona Stanislas , Kadende Mme Erica , Flavigny Aloyse , Plantier Isabelle , Detourmignies Laurence , Wemeau Mathieu , Dervite Isabelle , Dernivoix Kathy , Camille Mme , Denizart Ingrid , Lepretre Stéphane , Stamatoullas-Bastard Aspasia , Fontoura Marie-Laure , Jardin Fabrice , Menard Anne-Lise , Camus Vincent , Lanic Helene , Contentin Nathalie , Cardinael Nathalie , Lemasle-Hue Emilie , Alani Mustafa , Lebreton Pierre , Atia Youcef , Bilger Karin , Ledoux Marie-Pierre , Sonntag Cécile , Collin Camille , Tavernier Emmanuelle , Guyotat Denis , Soglu Gilbert , Le Jeune Caroline , Cornillon Jérôme , Durieux Coralie , Lavoué Céline , Miler Dorante , Huguet Françoise , Tavitian Suzanne , Soldan Justine , Rousselot Philippe , Rigaudeau Sophie , Philippe Laure , Lambert Juliette , Besson Caroline , Cabannes Aurélie , Longval Thomas , Taksin Anne-Laure , Bah Mariama , BeulayGue Anaïs , Doubek Michael , Folber Frantisek , Hrabovsky Stepan , Brzonova Jana , Vejsadova Hana , Salek Cyril , Novotova Elena , Mertova Jolana , Brzonova Jana , Vejsadova Hana , Wartiovaara-Kautto Ulla , Salonen Minna , Vaalas Saara 
Published: October 2024

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.