Efficacy of the Combination of Gemtuzumab-Ozogamicin (Mylotarg(R)) and Cytarabine (GOCYT) in Childhood Myeloid Leukemia: A Compassionate Use Based Review in France.
Authors: Brethon Benoit , Yakouben Karima , Oudot Caroline , Boutard Patrick , Bruno Benedicte , Jerome Cecile , Nelken Brigitte , de Lumley Lionel , Bertrand Yves , Dalle Jean-Hugues , Leblanc Thierry , Baruchel Andre 
Published: October 2019

Abstract
The use of Gemtuzumab-Ozogamicin (GO), an anti-CD33 monoclonal antibody, is associated to a 20–30% response rate in refractory/relapsed AML. We have reviewed the efficacy and the tolerance of a combination of GO plus cytarabine (GOCYT) given to children with refractory/relapsed AML in order to improve the response rate. This retrospective analysis includes 17 children (9M, 8F) who received the same induction schedule on a compassionate-use basis between may 2004 and june 2006: GO 3 mg/m2/d D1, D4, D7 plus cytarabine 100 mg/m2/d CIV for 7 days. In addition, 6 patients received a consolidation course with GO 3 mg/m2 D1 plus cytarabine 100 mg/m2/d D1 to D7 and 1 patient received GO 3 mg/m2 monthly for 4 doses. Median age at diagnosis of AML is 4.5 y (0.4–16.7). The patient distribution is: de novo AML: 13; biclonal (T and myeloid) acute leukemia: 1; erythremia: 1; t-AML: 2. Initial caryotype was unfavourable in 6 cases, intermediate in 9 and favourable in 2. Patient’s status at GOCYT start were as follows: 2 pts refractory to 1st line therapy (t-AML: 1, M7: 1); 8 pts in refractory first relapse (median time to relapse: 7.25 m, 5–19); 6 pts in relapse after BMT (median time to relapse: 13.5 m, 10.5–111); 1 untreated pt (del(5q) t-AML). CD33 expression was positive in all cases. The median time between initial diagnosis and GOCYT administration is 11.5 m (3–116). MFU is 5 months (1–21). Ten responses were obtained after GOCYT induction (59%): CR: 2, CRp: 4 and PR: 4. Noteworthy, 3 of 7 responders who received a consolidation course with GO improved their response (PR to CR: 2, PR to CRp: 1). Lastly, a subsequent BMT could be performed in 7 responders. Six pts were in leukemic failure and 1 pt died from invasive aspergillosis without bone marrow evaluation. Grade 3 and 4 side effects were: hematologic (17, 100%); documented infections (5): invasive aspergillosis (2 including one responder), pulmonary reactivation of aspergillosis (1), streptococcus oralis septicemia (1), candida kefyr septicemia (1); fever and neutropenia without documented infection (6); hyperbilirubinemia (1); hypertransaminasemia (1); sinusoidal obstruction syndrome SOS (0). Among the 7 patients alive at point date, 6 were responders to GOCYT.
Conclusion: a high response rate (59%) was objectived in children with heavily pre-treated refractory/relapsed AML allowing a subsequent BMT in 7. A consolidation course improved the quality of the response in some cases. Despite the limitations of this study, the response rate seems higher than the one observed in phase I–II or compassionate-use pediatric studies using GO alone. No unexpected toxicity was seen. Remarkably, no SOS was observed despite previous BMT in 8 out of the 17 children and a second BMT was feasible in responding pts. GOCYT should be tested prospectively in a largest pediatric AML population.