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Campini Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009540","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Blood &amp; Cancer"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The treatment paradigm for patients with relapsed\/refractory B\u2010cell acute lymphoblastic leukemia (rrALL) has been revolutionized given recent clinical trials demonstrating remarkable success of immunotherapies and leading to drug approvals by United States and European agencies. We report experience with commercial blinatumomab and inotuzumab use at two North American pediatric oncology centers in children and adolescents\/young adults with B\u2010ALL.<\/jats:p><\/jats:sec><jats:sec><jats:title>Procedure<\/jats:title><jats:p>Patients 0\u201025 years old treated with the CD19 \u00d7 CD3 bispecific T cell\u2010engaging antibody blinatumomab and\/or the CD22 antibody\u2010drug conjugate inotuzumab from January 1, 2010, to June 1, 2018, were eligible. Disease status included relapsed B\u2010ALL in second or greater relapse, primary chemotherapy\u2010refractory B\u2010ALL, or B\u2010ALL complicated by severe infection precluding delivery of conventional chemotherapy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified 27 patients who received blinatumomab and\/or inotuzumab outside of clinical trials during the study period. Four of the 13 patients (31%) with relapsed disease achieved minimal residual disease (MRD)\u2010negative remission, and five patients (39%) underwent hematopoietic stem cell transplant (HSCT). In the 12 patients with primary chemorefractory B\u2010ALL treated with immunotherapy, 11 (92%) achieved MRD\u2010negative remission as assessed by flow cytometry; 10 patients (83%) underwent subsequent HSCT. Two patients with B\u2010ALL in MRD\u2010negative remission received blinatumomab due to severe infection and remained in remission after chemotherapy continuation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Blinatumomab and inotuzumab can induce deep remissions in patients with rrALL and facilitate subsequent HSCT or other cellular therapies. Blinatumomab can also serve as an effective bridging therapy during severe infection. The optimal timing, choice of immunotherapeutic agent(s), and duration of responses require further investigation via larger\u2010scale clinical trials.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pbc.28718","type":"journal-article","created":{"date-parts":[[2020,10,24]],"date-time":"2020-10-24T16:44:36Z","timestamp":1603557876000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Clinical utilization of blinatumomab and inotuzumab immunotherapy in children with relapsed or refractory B\u2010acute lymphoblastic leukemia"],"prefix":"10.1002","volume":"68","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3867-8840","authenticated-orcid":false,"given":"Cristina F.","family":"Contreras","sequence":"first","affiliation":[{"name":"Children's Hospital of Philadelphia Division of Oncology and Center for Childhood Cancer Research  Philadelphia 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Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7032-4623","authenticated-orcid":false,"given":"Elliot","family":"Stieglitz","sequence":"additional","affiliation":[{"name":"San Francisco Benioff Children's Hospital and School of Medicine Pediatrics Division of Hematology\u2010Oncology University of California  San Francisco California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1327-1662","authenticated-orcid":false,"given":"Sarah K.","family":"Tasian","sequence":"additional","affiliation":[{"name":"Children's Hospital of Philadelphia Division of Oncology and Center for Childhood Cancer Research  Philadelphia Pennsylvania"},{"name":"Department of Pediatrics and Abramson Cancer Center University of Pennsylvania Perelman School of Medicine  Philadelphia 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