Effect of Postreinduction Therapy Consolidation With Blinatumomab vs Chemotherapy on Disease-Free Survival in Children, Adolescents, and Young Adults With First Relapse of B-Cell Acute Lymphoblastic Leukemia

Brown, Patrick; Ji, Lingyun; Xu, Xinxin; Devidas, Meenakshi; Hogan, Laura; Borowitz, Michael J.; Raetz, Elizabeth A.; Zugmaier, Gerhard; Sharon, Elad; Bernhardt, Melanie Brooke; Terezakis, Stephanie A.; Gore, Lia; Whitlock, James A.; Pulsipher, Michael A.; Hunger, Stephen P.; Loh, Mignon L.

doi:10.1001/jama.2021.0669

Cited by 197 publications

(204 citation statements)

References 28 publications

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“…The main adverse effects are cytokine release syndrome and neurotoxicity, which coincide with T cell activation. Two randomized studies in children, adolescents, and young adults with intermediate-risk or high-risk relapsed/refractory B-ALL showed blinatumomab to have benefits over intensive consolidation chemotherapy [ 129 , 130 ]. The loss of CD19 expression is a major mechanism of resistance to blinatumomab treatment and is also observed with CAR T cell therapy.…”

Section: Emerging Therapy: Immunotherapymentioning

confidence: 99%

Advances in the Diagnosis and Treatment of Pediatric Acute Lymphoblastic Leukemia

Inaba

Pui

2021

JCM

101

105

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The outcomes of pediatric acute lymphoblastic leukemia (ALL) have improved remarkably during the last five decades. Such improvements were made possible by the incorporation of new diagnostic technologies, the effective administration of conventional chemotherapeutic agents, and the provision of better supportive care. With the 5-year survival rates now exceeding 90% in high-income countries, the goal for the next decade is to improve survival further toward 100% and to minimize treatment-related adverse effects. Based on genome-wide analyses, especially RNA-sequencing analyses, ALL can be classified into more than 20 B-lineage subtypes and more than 10 T-lineage subtypes with prognostic and therapeutic implications. Response to treatment is another critical prognostic factor, and detailed analysis of minimal residual disease can detect levels as low as one ALL cell among 1 million total cells. Such detailed analysis can facilitate the rational use of molecular targeted therapy and immunotherapy, which have emerged as new treatment strategies that can replace or reduce the use of conventional chemotherapy.

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Section: Emerging Therapy: Immunotherapymentioning

confidence: 99%

Advances in the Diagnosis and Treatment of Pediatric Acute Lymphoblastic Leukemia

Inaba

Pui

2021

JCM

101

105

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“…The results of both phase III RCTs in children with first relapse of ALL confirm the superiority of blinatumomab in achieving MRD-negativity before HSCT and even show evidence for an advantage in overall survival [38,39], while inducing less severe adverse events compared to conventional chemotherapy. These results definitely warrant the inclusion of blinatumomab into relapse protocols before HSCT.…”

Section: Discussionmentioning

confidence: 61%

“…In newly published RCTs, Brown and colleagues describe blinatumomab-related adverse events with overall 22% CRS, 11% encephalopathy and 4% seizures but only one case of grade ≥3 CRS or seizure each and two cases of higher-grade encephalopathy. Other rates of notable serious adverse events were much less common in the blinatumomab group compared to the chemotherapy group: infection (15% vs. 65%), febrile neutropenia (5% vs. 58%), sepsis (2% vs. 27%) and mucositis (1% vs. 28%) [38].…”

Section: Adverse Eventsmentioning

confidence: 92%

“…In March 2021, the first results of two randomized controlled trials investigating blinatumomab in pediatric patients with ALL were published back to back in JAMA. Brown and colleagues describe the effect of postreinduction therapy consolidation with blinatumomab versus chemotherapy in patients with first relapse of ALL [38]. All patients received a 4-week reinduction chemotherapy course, followed by randomized assignment to receive two cycles of blinatumomab or two cycles of multiagent chemotherapy, each followed by HSCT.…”

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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“…After the first cycle of randomized therapy, the MRD neg rate was 75% for the blinatumomab group vs. 32% for the chemotherapy group ( p < 0.001). Finally, for the blinatumomab group, 70% proceeded to allogeneic HCT, compared with 43% for the chemotherapy group ( p < 0.001) [ 96 ].…”

Section: New Therapeutic Options For Mrd Positive Allmentioning

confidence: 99%

MRD-Based Therapeutic Decisions in Genetically Defined Subsets of Adolescents and Young Adult Philadelphia-Negative ALL

Tosi

Spinelli

Leoncin

et al. 2021

Cancers

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In many clinical studies published over the past 20 years, adolescents and young adults (AYA) with Philadelphia chromosome negative acute lymphoblastic leukemia (Ph− ALL) were considered as a rather homogeneous clinico-prognostic group of patients suitable to receive intensive pediatric-like regimens with an improved outcome compared with the use of traditional adult ALL protocols. The AYA group was defined in most studies by an age range of 18–40 years, with some exceptions (up to 45 years). The experience collected in pediatric ALL with the study of post-induction minimal residual disease (MRD) was rapidly duplicated in AYA ALL, making MRD a widely accepted key factor for risk stratification and risk-oriented therapy with or without allogeneic stem cell transplantation and experimental new drugs for patients with MRD detectable after highly intensive chemotherapy. This combined strategy has resulted in long-term survival rates of AYA patients of 60–80%. The present review examines the evidence for MRD-guided therapies in AYA’s Ph− ALL, provides a critical appraisal of current treatment pitfalls and illustrates the ways of achieving further therapeutic improvement according to the massive knowledge recently generated in the field of ALL biology and MRD/risk/subset-specific therapy

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Effect of Postreinduction Therapy Consolidation With Blinatumomab vs Chemotherapy on Disease-Free Survival in Children, Adolescents, and Young Adults With First Relapse of B-Cell Acute Lymphoblastic Leukemia

Cited by 197 publications

References 28 publications

Advances in the Diagnosis and Treatment of Pediatric Acute Lymphoblastic Leukemia

Advances in the Diagnosis and Treatment of Pediatric Acute Lymphoblastic Leukemia

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

MRD-Based Therapeutic Decisions in Genetically Defined Subsets of Adolescents and Young Adult Philadelphia-Negative ALL

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