Inotuzumab ozogamicin as single agent in pediatric patients with relapsed and refractory acute lymphoblastic leukemia: results from a phase II trial.

Autor: Pennesi E; Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.; Department of Pediatric Oncology, Erasmus MC-Sophia Children's Hospital, Rotterdam, the Netherlands., Michels N; Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.; Department of Pediatric Oncology, Erasmus MC-Sophia Children's Hospital, Rotterdam, the Netherlands.; Oncode Institute, Utrecht, the Netherlands., Brivio E; Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.; Department of Pediatric Oncology, Erasmus MC-Sophia Children's Hospital, Rotterdam, the Netherlands., van der Velden VHJ; Department of Immunology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands., Jiang Y; Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands., Thano A; Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands., Ammerlaan AJC; Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.; Department of Pediatric Oncology, Erasmus MC-Sophia Children's Hospital, Rotterdam, the Netherlands., Boer JM; Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.; Oncode Institute, Utrecht, the Netherlands., Beverloo HB; Department of Clinical Genetics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands., Sleight B; Pfizer Inc, Groton, CT, USA., Chen Y; Pfizer Inc, Groton, CT, USA., Vormoor-Bürger B; Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands., Rives S; Pediatric Oncology and Hematology Department, Hospital Sant Joan de Déu de Barcelona, Barcelona, Spain.; Institut de Recerca Sant Joan de Déu, Barcelona, Spain., Bielorai B; Division of Pediatric Hematology and Oncology, Sheba Medical Center, Ramat-Gan, Israel., Rössig C; Pediatric Hematology and Oncology, University Children's Hospital Muenster, Münster, Germany., Petit A; Department of pediatric Hematology and Oncology, Hopital Armand Trousseau, APHP, Sorbonne Université, Paris, France., Rizzari C; Pediatric Hematology-Oncology Unit, Department of Pediatrics, MBBM Foundation, ASST Monza, University of Milano-Bicocca, Monza, Italy., Engstler G; St Anna Children's Hospital, Medical University of Vienna, Vienna, Austria., Starý J; Department of Pediatric Hematology and Oncology, University Hospital Motol, Prague, Czech Republic., Bautista Sirvent FJ; Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.; Department of Pediatric Oncology and Hematology, Hospital Niño Jesús, Madrid, Spain., Chen-Santel C; Department of Pediatrics, Division of Oncology and Hematology, Charité - Universitätsmedizin Berlin, Berlin, Germany.; Department of Pediatrics, Rostock University Medical Centre, Rostock, Germany., Bruno B; Pediatric Hematology, Hôpital Jeanne de Flandre, CHRU de Lille, Lille, France., Bertrand Y; Institute of Pediatric Hematology and Oncology, Civil Hospital of Lyon, Claude Bernard University, Lyon, France., Rialland F; Service Onco-Hématologie Pédiatrique, Hôpital Mère-Enfant, Nantes University Hospital, Nantes, France., Plat G; Service d'Hématologie-Immunologie-Oncologie, Hôpital des Enfants, CHU Toulouse, Toulouse, France., Reinhardt D; Department of Pediatric Oncology, Essen University Hospital, Essen, Germany., Vinti L; Department of Hematology, Oncology and of Cell and Gene Therapy, IRCCS Ospedale Pediatrico Bambino Gesú, Sapienza, University of Rome, Rome, Italy., Von Stackelberg A; Department of Pediatrics, Division of Oncology and Hematology, Charité - Universitätsmedizin Berlin, Berlin, Germany.; IntReALL study group, Berlin, Germany., Locatelli F; Department of Hematology, Oncology and of Cell and Gene Therapy, IRCCS Ospedale Pediatrico Bambino Gesú, Sapienza, University of Rome, Rome, Italy., Zwaan CM; Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands. c.m.zwaan@prinsesmaximacentrum.nl.; Department of Pediatric Oncology, Erasmus MC-Sophia Children's Hospital, Rotterdam, the Netherlands. c.m.zwaan@prinsesmaximacentrum.nl.
Jazyk: angličtina
Zdroj: Leukemia [Leukemia] 2022 Jun; Vol. 36 (6), pp. 1516-1524. Date of Electronic Publication: 2022 Apr 25.
DOI: 10.1038/s41375-022-01576-3
Abstrakt: Inotuzumab Ozogamicin is a CD22-directed antibody conjugated to calicheamicin, approved in adults with relapsed or refractory (R/R) B cell acute lymphoblastic leukemia (BCP-ALL). Patients aged 1-18 years, with R/R CD22 + BCP-ALL were treated at the RP2D of 1.8 mg/m 2 . Using a single-stage design, with an overall response rate (ORR) ≤ 30% defined as not promissing and ORR > 55% as expected, 25 patients needed to be recruited to achieve 80% power at 0.05 significance level. Thirty-two patients were enrolled, 28 were treated, 27 were evaluable for response. The estimated ORR was 81.5% (95%CI: 61.9-93.7%), and 81.8% (18/22) of the responding subjects were minimal residual disease (MRD) negative. The study met its primary endpoint. Median follow up of survivors was 16 months (IQR: 14.49-20.07). One year Event Free Survival was 36.7% (95% CI: 22.2-60.4%), and Overall Survival was 55.1% (95% CI: 39.1-77.7%). Eighteen patients received consolidation (with HSCT and/or CAR T-cells therapy). Sinusoidal obstructive syndrome (SOS) occurred in seven patients. MRD negativity seemed correlated to calicheamicin sensitivity in vitro, but not to CD22 surface expression, saturation, or internalization. InO was effective in this population. The most relevant risk was the occurrence of SOS, particularly when InO treatment was followed by HSCT.
(© 2022. The Author(s).)
Databáze: MEDLINE
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