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FDA Supplemental Approval: Blinatumomab for Treatment of Relapsed and Refractory Precursor B‐Cell Acute Lymphoblastic Leukemia

On July 11, 2017, the Food and Drug Administration granted approval for blinatumomab for the treatment of relapsed or refractory (R/R) precursor B‐cell acute lymphoblastic leukemia (ALL). Blinatumomab is a bispecific CD19‐directed CD3 T‐cell engager. The basis for the approval included results from...

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Autores principales: Pulte, E. Dianne, Vallejo, Jonathon, Przepiorka, Donna, Nie, Lei, Farrell, Ann T., Goldberg, Kirsten B., McKee, Amy E., Pazdur, Richard
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons, Inc. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6291336/
https://www.ncbi.nlm.nih.gov/pubmed/30018129
http://dx.doi.org/10.1634/theoncologist.2018-0179
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author Pulte, E. Dianne
Vallejo, Jonathon
Przepiorka, Donna
Nie, Lei
Farrell, Ann T.
Goldberg, Kirsten B.
McKee, Amy E.
Pazdur, Richard
author_facet Pulte, E. Dianne
Vallejo, Jonathon
Przepiorka, Donna
Nie, Lei
Farrell, Ann T.
Goldberg, Kirsten B.
McKee, Amy E.
Pazdur, Richard
author_sort Pulte, E. Dianne
collection PubMed
description On July 11, 2017, the Food and Drug Administration granted approval for blinatumomab for the treatment of relapsed or refractory (R/R) precursor B‐cell acute lymphoblastic leukemia (ALL). Blinatumomab is a bispecific CD19‐directed CD3 T‐cell engager. The basis for the approval included results from two clinical trials, TOWER and ALCANTARA. TOWER, a randomized trial comparing overall survival in patients with Philadelphia chromosome (Ph)‐negative R/R ALL receiving blinatumomab versus standard‐of‐care (SOC) chemotherapy, demonstrated a hazard ratio of 0.71 favoring blinatumomab (p = .012; median survival, 7.7 months with blinatumomab and 4.0 months with SOC chemotherapy). Complete remission (CR) rates were 34% for patients receiving blinatumomab and 16% for those receiving SOC. Adverse events were consistent with those observed in prior trials, with cytokine release syndrome and some neurologic events, including tremor, encephalopathy, peripheral neuropathy, and depression, observed more frequently in the blinatumomab arm, whereas neutropenia and infection were less common among patients receiving blinatumomab. Depression emerged as a rare but potentially severe neurologic event associated with blinatumomab. In ALCANTARA, a single‐arm trial of blinatumomab in patients with Ph‐positive R/R ALL, the CR rate was 31%, and adverse events were similar to those observed previously in Ph‐negative R/R ALL. These results support conversion from accelerated to regular approval of blinatumomab for R/R ALL and broadening of the intended population to include both Ph‐positive and Ph‐negative precursor B‐cell R/R ALL. IMPLICATIONS FOR PRACTICE. In TOWER, a randomized trial in patients with relapsed or refractory Philadelphia chromosome (Ph)‐negative precursor B‐cell acute lymphoblastic leukemia (ALL), treatment with blinatumomab showed superiority over conventional chemotherapy for complete remission (CR) rate (34% vs. 16%) and survival (3.7‐month improvement in median; hazard ratio, 0.71). In ALCANTARA, a single‐arm trial of blinatumomab for treatment of relapsed or refractory Ph‐positive precursor B‐cell ALL, the CR rate was 31%. Blinatumomab is now approved for treatment of relapsed or refractory precursor B‐cell ALL that is Ph positive or Ph negative.
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spelling pubmed-62913362018-12-13 FDA Supplemental Approval: Blinatumomab for Treatment of Relapsed and Refractory Precursor B‐Cell Acute Lymphoblastic Leukemia Pulte, E. Dianne Vallejo, Jonathon Przepiorka, Donna Nie, Lei Farrell, Ann T. Goldberg, Kirsten B. McKee, Amy E. Pazdur, Richard Oncologist Regulatory Issues: FDA On July 11, 2017, the Food and Drug Administration granted approval for blinatumomab for the treatment of relapsed or refractory (R/R) precursor B‐cell acute lymphoblastic leukemia (ALL). Blinatumomab is a bispecific CD19‐directed CD3 T‐cell engager. The basis for the approval included results from two clinical trials, TOWER and ALCANTARA. TOWER, a randomized trial comparing overall survival in patients with Philadelphia chromosome (Ph)‐negative R/R ALL receiving blinatumomab versus standard‐of‐care (SOC) chemotherapy, demonstrated a hazard ratio of 0.71 favoring blinatumomab (p = .012; median survival, 7.7 months with blinatumomab and 4.0 months with SOC chemotherapy). Complete remission (CR) rates were 34% for patients receiving blinatumomab and 16% for those receiving SOC. Adverse events were consistent with those observed in prior trials, with cytokine release syndrome and some neurologic events, including tremor, encephalopathy, peripheral neuropathy, and depression, observed more frequently in the blinatumomab arm, whereas neutropenia and infection were less common among patients receiving blinatumomab. Depression emerged as a rare but potentially severe neurologic event associated with blinatumomab. In ALCANTARA, a single‐arm trial of blinatumomab in patients with Ph‐positive R/R ALL, the CR rate was 31%, and adverse events were similar to those observed previously in Ph‐negative R/R ALL. These results support conversion from accelerated to regular approval of blinatumomab for R/R ALL and broadening of the intended population to include both Ph‐positive and Ph‐negative precursor B‐cell R/R ALL. IMPLICATIONS FOR PRACTICE. In TOWER, a randomized trial in patients with relapsed or refractory Philadelphia chromosome (Ph)‐negative precursor B‐cell acute lymphoblastic leukemia (ALL), treatment with blinatumomab showed superiority over conventional chemotherapy for complete remission (CR) rate (34% vs. 16%) and survival (3.7‐month improvement in median; hazard ratio, 0.71). In ALCANTARA, a single‐arm trial of blinatumomab for treatment of relapsed or refractory Ph‐positive precursor B‐cell ALL, the CR rate was 31%. Blinatumomab is now approved for treatment of relapsed or refractory precursor B‐cell ALL that is Ph positive or Ph negative. John Wiley & Sons, Inc. 2018-07-17 2018-11 /pmc/articles/PMC6291336/ /pubmed/30018129 http://dx.doi.org/10.1634/theoncologist.2018-0179 Text en Published 2018. This article is a U.S. Government work and is in the public domain in the USA
spellingShingle Regulatory Issues: FDA
Pulte, E. Dianne
Vallejo, Jonathon
Przepiorka, Donna
Nie, Lei
Farrell, Ann T.
Goldberg, Kirsten B.
McKee, Amy E.
Pazdur, Richard
FDA Supplemental Approval: Blinatumomab for Treatment of Relapsed and Refractory Precursor B‐Cell Acute Lymphoblastic Leukemia
title FDA Supplemental Approval: Blinatumomab for Treatment of Relapsed and Refractory Precursor B‐Cell Acute Lymphoblastic Leukemia
title_full FDA Supplemental Approval: Blinatumomab for Treatment of Relapsed and Refractory Precursor B‐Cell Acute Lymphoblastic Leukemia
title_fullStr FDA Supplemental Approval: Blinatumomab for Treatment of Relapsed and Refractory Precursor B‐Cell Acute Lymphoblastic Leukemia
title_full_unstemmed FDA Supplemental Approval: Blinatumomab for Treatment of Relapsed and Refractory Precursor B‐Cell Acute Lymphoblastic Leukemia
title_short FDA Supplemental Approval: Blinatumomab for Treatment of Relapsed and Refractory Precursor B‐Cell Acute Lymphoblastic Leukemia
title_sort fda supplemental approval: blinatumomab for treatment of relapsed and refractory precursor b‐cell acute lymphoblastic leukemia
topic Regulatory Issues: FDA
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6291336/
https://www.ncbi.nlm.nih.gov/pubmed/30018129
http://dx.doi.org/10.1634/theoncologist.2018-0179
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