Effect of Blinatumomab vs Chemotherapy on Event-Free Survival Among Children With High-risk First-Relapse B-Cell Acute Lymphoblastic Leukemia: A Randomized Clinical Trial
Franco Locatelli,Gerhard Zugmaier,Carmelo Rizzari,J. Morris,Bernd Gruhn,Thomas Klingebiel,Rosanna Parasole,Christin Linderkamp,Christian Flotho,Arnaud Petit,Concetta Micalizzi,Noemi Mergen,Abeera Mohammad,William Kormany,Cornelia Eckert,Anja Möricke,Mary Sartor,Ondrej Hrusak,Christina Peters,Vaskar Saha,Luciana Vinti,Arend von Stackelberg +21 more
TLDR
In this article, the authors evaluated event-free survival in children with high-risk first-relapse B-ALL after a third consolidation course with blinatumomab vs consolidation chemotherapy before allogeneic hematopoietic stem cell transplant.Abstract:
Importance Blinatumomab is a CD3/CD19-directed bispecific T-cell engager molecule with efficacy in children with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL). Objective To evaluate event-free survival in children with high-risk first-relapse B-ALL after a third consolidation course with blinatumomab vs consolidation chemotherapy before allogeneic hematopoietic stem cell transplant. Design, setting, and participants In this randomized phase 3 clinical trial, patients were enrolled November 2015 to July 2019 (data cutoff, July 17, 2019). Investigators at 47 centers in 13 countries enrolled children older than 28 days and younger than 18 years with high-risk first-relapse B-ALL in morphologic complete remission (M1 marrow, Intervention Patients were randomized to receive 1 cycle of blinatumomab (n = 54; 15 μg/m2/d for 4 weeks, continuous intravenous infusion) or chemotherapy (n = 54) for the third consolidation. Main outcomes and measures The primary end point was event-free survival (events: relapse, death, second malignancy, or failure to achieve complete remission). The key secondary efficacy end point was overall survival. Other secondary end points included minimal residual disease remission and incidence of adverse events. Results A total of 108 patients were randomized (median age, 5.0 years [interquartile range {IQR}, 4.0-10.5]; 51.9% girls; 97.2% M1 marrow) and all patients were included in the analysis. Enrollment was terminated early for benefit of blinatumomab in accordance with a prespecified stopping rule. After a median of 22.4 months of follow-up (IQR, 8.1-34.2), the incidence of events in the blinatumomab vs consolidation chemotherapy groups was 31% vs 57% (log-rank P Conclusions and relevance Among children with high-risk first-relapse B-ALL, treatment with 1 cycle of blinatumomab compared with standard intensive multidrug chemotherapy before allogeneic hematopoietic stem cell transplant resulted in an improved event-free survival at a median of 22.4 months of follow-up. Trial registration ClinicalTrials.gov Identifier: NCT02393859.read more
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Journal ArticleDOI
Advances in the Diagnosis and Treatment of Pediatric Acute Lymphoblastic Leukemia.
TL;DR: Detailed analysis of minimal residual disease can detect levels as low as one ALL cell among 1 million total cells, and 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.
Journal ArticleDOI
Blinatumomab Nonresponse and High-Disease Burden Are Associated With Inferior Outcomes After CD19-CAR for B-ALL
TL;DR: In this paper , the authors conducted a multicenter, retrospective review of children and young adults with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL) who received CD19-CAR between 2012 and 2019.
Journal ArticleDOI
Blinatumomab Nonresponse and High-Disease Burden Are Associated With Inferior Outcomes After CD19-CAR for B-ALL.
Regina M. Myers,Agne Taraseviciute,Agne Taraseviciute,Seth M. Steinberg,Adam J. Lamble,Jennifer Sheppard,Bonnie Yates,Alexandra E. Kovach,Brent L. Wood,Michael J. Borowitz,Maryalice Stetler-Stevenson,Constance M. Yuan,Vinodh Pillai,Toni Foley,Perry Chung,Lee Chen,Daniel W. Lee,Colleen Annesley,Amanda M. DiNofia,Stephan A. Grupp,Samuel John,Deepa Bhojwani,Patrick A. Brown,Theodore W. Laetsch,Theodore W. Laetsch,Lia Gore,Rebecca Gardner,Susan R. Rheingold,Michael A. Pulsipher,Nirali N. Shah +29 more
TL;DR: PURPOSECD19-targeted chimeric antigen receptor T cells (CD19-CAR) and blinatumomab effectively induce remission in relapsed or refractory B-cell acute lymphoblastic leukemia (ALL) but are also asso...
Journal ArticleDOI
Anti-CCR9 Chimeric Antigen Receptor T cells for T Cell Acute Lymphoblastic Leukemia.
Paul Maciocia,Patrycja Wawrzyniecka,Nicola Maciocia,Amy Burley,Thaneswari Karpanasamy,Sam Devereaux,Malika Hoekx,David O'Connor,Theresa E. Leon,Tanya Rapoz-D'Silva,Rachael Pocock,Sunniyat Rahman,Giuseppe Gritti,Diana C. Yánez,Susan Ross,Tessa Crompton,Owen Williams,Lydia Lee,Martin Pule,Marc R. Mansour +19 more
TL;DR: It is demonstrated that the chemokine receptor CCR9 is expressed in >70% of cases of T-ALL, including >85% or relapsed/ refractory disease, and only on a small fraction of normal T cells, and chimeric antigen receptor (CAR)-T cells targeting CCR8 are resistant to fratricide and have potent anti-leukemic activity both in vitro and in vivo.
Journal ArticleDOI
Blinatumomab in Pediatric Acute Lymphoblastic Leukemia-From Salvage to First Line Therapy (A Systematic Review).
Manon Queudeville,Martin Ebinger +1 more
TL;DR: In this article, a systematic review discusses all published results for blinatumomab in children as well as all ongoing clinical trials in R/R-ALL and concludes that the use of BLINATOMAB is beneficial for patients with a high risk of severe chemotherapy-associated toxicities.
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