Clinical utilization of blinatumomab and inotuzumab immunotherapy in children with relapsed or refractory B‐acute lymphoblastic leukemia

Abstract

Background: The treatment paradigm for patients with relapsed/refractory B-cell 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 BALL. Procedure: Patients 0-25 years old treated with the CD19 × CD3 bispecific T cellengaging antibody blinatumomab and/or the CD22 antibody-drug conjugate inotuzumab from January 1, 2010, to June 1, 2018, were eligible. Disease status included relapsed BALL in second or greater relapse, primary chemotherapy-refractory BALL , or BALL complicated by severe infection precluding delivery of conventional chemotherapy. Results: 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)-negative remission, and five patients (39%) underwent hematopoietic stem cell transplant (HSCT). In the 12 patients with primary chemorefractory BALL treated with immunotherapy, 11 (92%) achieved MRD-negative remission as assessed by flow cytometry; 10 patients (83%) underwent subsequent HSCT. Two patients with BALL in MRD-negative remission received blinatumomab due to severe infection and remained in remission after chemotherapy continuation. Conclusions: 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-scale clinical trials.

Blinatumomab in Children and Adolescents with Relapsed/Refractory B Cell Precursor Acute Lymphoblastic Leukemia: A Real-Life Multicenter Retrospective Study in Seven AIEOP (Associazione Italiana di Ematologia e Oncologia Pediatrica) Centers

“…Comparable data were reported by Contreras et al [ 24 ]—neurological complications accounted for 22% (4/18 patients), of which only one was grade 4, while a lower percentage of CRS was described (6/18 patients, 33%).…”

“…In the German [ 16 ] retrospective analysis, the median OS for all patients was 11.1 months (0.2–113 months), and median RFS was 6.17 months (0–18 months), with a total CR rate of 34%. Contreras et al [ 24 ] reported 18 patients treated with commercial blinatumomab; 12 of them achieved a CR (both morphological and MRD). In the Spanish study [ 25 ] 8 of 15 children (53%) reached CR with sustained MRD negativity after one cycle; median OS and RFS were 22 (range 3–41) and 8.5 months (range 0–17), respectively.…”

Invasive Fungal Diseases in Children with Hematological Malignancies Treated with Therapies That Target Cell Surface Antigens: Monoclonal Antibodies, Immune Checkpoint Inhibitors and CAR T-Cell Therapies

“…A retrospective study of r/r precursor B-cell ALL in pediatric patients under compassionate use with InO and blinatumomab recorded two severe infections (6.5%) that led to death [ 78 ]. Likewise, another retrospective study of children with r/r B-ALL treated with InO reported two events of severe infection (7.4%; one with IFD i.e., mucor-mycosis), that survived following bridging therapy with blinatumomab [ 19 ].…”

Blinatumomab in Pediatric Acute Lymphoblastic Leukemia—From Salvage to First Line Therapy (A Systematic Review)

“…Colleagues from Spain describe 27 patients treated with blinatumomab and/or inotuzumab, demonstrating that both immunotherapies can induce deep remissions, and blinatumomab can serve as an effective bridging therapy during severe infections [33]. Colleagues from Greece published their experience with nine patients with R/R ALL [34].…”