Inotuzumab ozogamicin in pediatric patients with relapsed/refractory acute lymphoblastic leukemia

Abstract

Although inotuzumab ozogamicin (InO) is recognized as an effective agent in relapsed acute lymphoblastic leukemia (ALL) in adults, data on safety and efficacy in pediatric patients are scarce. We report the use of InO in 51 children with relapsed/refractory ALL treated in the compassionate use program. In this heavily pretreated cohort, complete remission was achieved in 67% of patients with overt marrow disease. The majority (71%) of responders were negative for minimal residual disease. Responses were observed irrespective of cytogenetic subtype or number or type of prior treatment regimens. InO was well-tolerated; grade 3 hepatic transaminitis or hyperbilirubinemia were noted in 6 (12%) and grade 3/4 infections in 11 (22%) patients. No patient developed sinusoidal obstruction syndrome (SOS) during InO therapy; however, 11 of 21 (52%) patients who underwent hematopoietic stem cell transplantation (HSCT) following InO developed SOS. Downregulation of surface CD22 was detected as a possible escape mechanism in three patients who developed a subsequent relapse after InO. We conclude that InO is a well-tolerated, effective therapy for children with relapsed ALL and prospective studies are warranted. Identification of risk factors for developing post-HSCT SOS and strategies to mitigate this risk are ongoing.

Fig. 1

EFS (a) and OS (b). The 12-month EFS and OS rates for the entire cohort of 51 patients were 23.4 ± 7.5% and 36.3 ± 9.3%, respectively

Fig. 2

CD22 expression at relapse post-InO. CD22 expression in two patients evaluated pre- and post- InO and in one patient post-InO. CD22 is uniformly expressed on >99% B-lymphoblastic leukemia cells prior to InO (a, d); however, CD22 expression is diminished or absent (b, c, e) or absent in a subset of lymphoblasts (f) after InO