Initial Experience With CMC-544 (Inotuzumab Ozogamicin) in Pediatric Patients With Relapsed B-Cell Acute Lymphoblastic Leukemia

Survival is poor in pediatric patients with relapsed or refractory acute B-cell lymphoblastic leukemia (ALL) and therapeutic options are limited. CMC-544 (inotuzumab ozogamicin) has shown significant activity in adult patients with relapsed and refractory ALL. We evaluated CMC-544 in pediatric patients with multiply relapsed ALL. Five children 4-15 years old with relapsed, CD 22 positive B-cell ALL were enrolled on a phase II non-randomized trial of CMC-544. CMC-544 was initially administered at 1.3mg/m(2) every 3 weeks. The dose then increased to 1.8mg/m(2) every 3 weeks. Subsequently, a weekly schedule of CMC-544 given as 0.8mg/m(2) on day 1 followed by 0.5mg/m(2) on days 8 and 15 was administered. All five patients had refractory relapsed B-cell ALL. Lymphoblasts for all patients highly expressed CD22. Four patients had two or more relapses before starting the study drug. One patient achieved a complete remission in the bone marrow and normal peripheral counts, and two patients achieved bone marrow morphologic remission with absolute neutrophils >1,000/mu l but platelets <100,000/mu l. Two patients had no response to the drug. Toxicities consisted of fever, sepsis, and liver enzyme elevation. Single agent CMC-544 given at the single dose of 1.8mg/m(2) every 3 weeks or given as a split, weekly dose was generally well tolerated considering the inherent risks in this population of patients and showed promising activity in pediatric patients with relapsed and refractory ALL. Pediatr Blood Cancer 2014;61:369-372. (c) 2013 Wiley Periodicals, Inc.