TY - JOUR
T1 - Inotuzumab ozogamicin in pediatric patients with relapsed/refractory acute lymphoblastic leukemia
AU - Bhojwani, Deepa
AU - Sposto, Richard
AU - Shah, Nirali N.
AU - Rodriguez, Vilmarie
AU - Yuan, Constance
AU - Stetler-Stevenson, Maryalice
AU - O’Brien, Maureen M.
AU - McNeer, Jennifer L.
AU - Quereshi, Amrana
AU - Cabannes, Aurelie
AU - Schlegel, Paul
AU - Rossig, Claudia
AU - Dalla-Pozza, Luciano
AU - August, Keith
AU - Alexander, Sarah
AU - Bourquin, Jean Pierre
AU - Zwaan, Michel
AU - Raetz, Elizabeth A.
AU - Loh, Mignon L.
AU - Rheingold, Susan R.
N1 - Publisher Copyright:
© 2018, The Author(s).
PY - 2019/4/1
Y1 - 2019/4/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85054408147&partnerID=8YFLogxK
U2 - 10.1038/s41375-018-0265-z
DO - 10.1038/s41375-018-0265-z
M3 - Article
C2 - 30267011
AN - SCOPUS:85054408147
SN - 0887-6924
VL - 33
SP - 884
EP - 892
JO - Leukemia
JF - Leukemia
IS - 4
ER -