A phase 1b study of blinatumomab in Japanese children with relapsed/refractory B-cell precursor acute lymphoblastic leukemia

Horibe, Keizo; Morris, Joan; Tuglus, Catherine; Santos, Cédric Dos; Kalabus, James; Anderson, Abraham; Goto, Hiroaki; Ogawa, Chitose

doi:10.1007/s12185-020-02907-9

Cited by 10 publications

(25 citation statements)

References 16 publications

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“…Overall, adverse events are much less common under blinatumomab compared to conventional chemotherapy [38,39]. Additionally, even specific blinatumomab-related toxicities, such as CRS and neurotoxicity, only rarely necessitate the interruption of therapy [20,31,35]. This observation makes blinatumomab an ideal drug for selected use in vulnerable patients, such as children with Down syndrome, with a high risk for chemotherapy-related mortality [50] or other patients experiencing overwhelming toxicities [29].…”

Section: Discussionmentioning

confidence: 99%

“…A successful bridging to HSCT was feasible in 5/9 patients (55.6%), but the median RFS and OS remained low (3.0 and 8.7 months, respectively). Correspondingly, colleagues in Japan conducted an open-label phase 1b study in nine patients [35]. No dose-limiting toxicities were reported; morphological remission within the first two treatment cycles was 56%; one patient had a minimal residual disease response.…”

Section: Efficacymentioning

confidence: 99%

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

Queudeville

Ebinger

2021

JCM

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Acute lymphoblastic leukemia is by far the most common malignancy in children, and new immunotherapeutic approaches will clearly change the way we treat our patients in future years. Blinatumomab is a bispecific T-cell-engaging antibody indicated for the treatment of relapsed/refractory acute lymphoblastic leukemia (R/R-ALL). The use of blinatumomab in R/R ALL has shown promising effects, especially as a bridging tool to hematopoietic stem cell transplantation. For heavily pretreated patients, the response to one or two cycles of blinatumomab ranges from 34% to 66%. Two randomized controlled trials have very recently demonstrated an improved reduction in minimal residual disease as well as an increased survival for patients treated with blinatumomab compared to standard consolidation treatment in first relapse. Current trials using blinatumomab frontline for high-risk patients or as a consolidation treatment post-transplant will show whether efficacy is even higher in less heavily pretreated patients. Due to the distinct pattern of adverse events compared to high-dose conventional chemotherapy, blinatumomab could play an important role for patients with a risk for severe chemotherapy-associated toxicities. This systematic review discusses all published results for blinatumomab in children as well as all ongoing clinical trials.

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Section: Discussionmentioning

confidence: 99%

Section: Efficacymentioning

confidence: 99%

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

Queudeville

Ebinger

2021

JCM

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“…One open-label clinical trial enrolled 9 Japanese children with B-ALL, who received blinatumomab for 4 weeks (at a dose of 5 µg/m2/day for week 1 and followed by a dose of 15 µg/m2/day for weeks 2-4), followed by a treatment-free interval of 2-week. In this study a total of 7 neurologic events and 5 CRS were identified (15). The other open-label trial enrolled children aged < 18 years with relapsed/refractory (B-ALL), with a total of 70 patients that received the recommended dosage using 6weeks treatment cycles.…”

Section: Phase / Clinical Trialsmentioning

confidence: 99%

The safety of blinatumomab in pediatric patients with acute lymphoblastic leukemia: A systematic review and meta-analysis

et al. 2022

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BackgroundBlinatumomab is a bispecific CD19-directed CD3 T-cell engager that has proven efficacy in children with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL). Despite its efficacy, it has also been associated with the development of potentially serious adverse events such as the cytokine release syndrome (CRS) and neurologic events. The present meta-analysis aimed to assess the safety profile of blinatumomab in terms of serious adverse events, CRS, and neurologic events (such as seizure and encephalopathy) in pediatric patients with B-cell ALL.Methods and findingsA systematic review was conducted in Pubmed up to December 10, 2021 to retain pediatric clinical trials on blinatumomab. A random effect meta-analysis approach was used. This study followed the PRISMA statement. Four out of the 255 initial references were selected, of which 2 were phase 1/2 clinical trials and 2 phase 3 clinical trials. Blinatumomab was associated with a lower risk of serious adverse events (Risk ratio RR, 0.56; 95% CI, 0.32–0.99), febrile neutropenia (RR, 0.13; 95% CI, 0.06–0.26), infection (RR, 0.40; 95% CI, 0.29–0.56), and grade ≥ 3 adverse events (RR, 0.79; 95% CI, 0.67–0.93) compared to chemotherapy. No difference in the risk of CRS (RR, 8.37; 95% CI, 0.27–260.97) and seizure (RR, 6.43; 95% CI, 0.79–53.08) was observed between groups, while for encephalopathy a higher risk was associated with blinatumomab compared to chemotherapy (RR, 8.90; 95% CI, 1.08–73.29).ConclusionOur data support the good safety profile of bliantumomab in treating pediatric patients with B-ALL.

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“…In pediatric patients with ALL receiving blinatumomab, neurologic toxicities have occurred in approximately 32% of patients in published reports (137)(138)(139)(140)(141)(142)(143)(144)(145)(146)(147)(148). Most events occur early within the first treatment cycle and are usually associated with the start of the infusion or during the dose escalation phase.…”

Section: Neurotoxicity Experience In Blinatumomabmentioning

confidence: 99%

“…The most common neurologic manifestations in pediatric ALL patients are headache and tremor. Grade 3 or higher neurologic toxicities following initiation of blinatumomab occur in approximately 5% of pediatric patients and included seizures, encephalopathy, tremor, neuralgia, depressed level of consciousness, dysarthria, agitation, cranial nerve disorder, somnolence, and headaches (137)(138)(139)(140)(141)(142)(143)(144)(145)(146)(147)(148). It is important to note that there is extremely limited data (case reports) of patients with active central nervous system ALL receiving blinatumomab as these patients were excluded from clinical trials, thus the incidence of neurotoxicity in this population is unknown.…”

Section: Neurotoxicity Experience In Blinatumomabmentioning

confidence: 99%

Immunotherapy Associated Neurotoxicity in Pediatric Oncology

et al. 2022

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Novel immunotherapies are increasingly being employed in pediatric oncology, both in the upfront and relapsed/refractory settings. Through various mechanisms of action, engagement and activation of the immune system can cause both generalized and disease site-specific inflammation, leading to immune-related adverse events (irAEs). One of the most worrisome irAEs is that of neurotoxicity. This can present as a large spectrum of neurological toxicities, including confusion, aphasia, neuropathies, seizures, and/or death, with variable onset and severity. Earlier identification and treatment, generally with corticosteroids, remains the mainstay of neurotoxicity management to optimize patient outcomes. The pathophysiology of neurotoxicity varies across the different therapeutic strategies and remains to be elucidated in most cases. Furthermore, little is known about long-term neurologic sequelae. This review will focus on neurotoxicity seen with the most common immunotherapies used in pediatric oncology, including CAR T cell therapy, alternative forms of adoptive cell therapy, antibody therapies, immune checkpoint inhibitors, and tumor vaccines. Herein we will discuss the incidence, pathophysiology, symptomatology, diagnosis, and management strategies currently being utilized for immunotherapy-associated neurotoxicity with a focus on pediatric specific considerations.

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A phase 1b study of blinatumomab in Japanese children with relapsed/refractory B-cell precursor acute lymphoblastic leukemia

Cited by 10 publications

References 16 publications

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

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

The safety of blinatumomab in pediatric patients with acute lymphoblastic leukemia: A systematic review and meta-analysis

Immunotherapy Associated Neurotoxicity in Pediatric Oncology

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