title: FDA Approval: Blinatumomab.
abstract: On December 3, 2014, the FDA granted accelerated approval of blinatumomab (Blincyto; Amgen, Inc.) for treatment of Philadelphia chromosome-negative relapsed or refractory precursor B-cell acute lymphoblastic leukemia (R/R ALL). Blinatumomab is a recombinant murine protein that acts as a bispecific CD19-directed CD3 T-cell engager. The basis for the approval was a single-arm trial with 185 evaluable adults with R/R ALL. The complete remission (CR) rate was 32% [95% confidence interval (CI), 26%-40%], and the median duration of response was 6.7 months. A minimal residual disease response was achieved by 31% (95% CI, 25%-39%) of all patients. Cytokine release syndrome and neurologic events were serious toxicities that occurred. Other common (>20%) adverse reactions were pyrexia, headache, edema, febrile neutropenia, nausea, tremor, and rash. Neutropenia, thrombocytopenia, and elevated transaminases were the most common (>10%) laboratory abnormalities related to blinatumomab. A randomized trial is required in order to confirm clinical benefit.
authors.affiliation: Center for Drug Evaluation and Research, FDA, Silver Spring, Maryland. donna.przepiorka@fda.hhs.gov.
authors.forename: Donna
authors.initials: D
authors.lastname: Przepiorka
authors.affiliation: Center for Drug Evaluation and Research, FDA, Silver Spring, Maryland.
authors.forename: Chia-Wen
authors.initials: CW
authors.lastname: Ko
authors.affiliation: Center for Drug Evaluation and Research, FDA, Silver Spring, Maryland.
authors.forename: Albert
authors.initials: A
authors.lastname: Deisseroth
authors.affiliation: Center for Drug Evaluation and Research, FDA, Silver Spring, Maryland.
authors.forename: Carolyn L
authors.initials: CL
authors.lastname: Yancey
authors.affiliation: Center for Drug Evaluation and Research, FDA, Silver Spring, Maryland.
authors.forename: Reyes
authors.initials: R
authors.lastname: Candau-Chacon
authors.affiliation: Center for Drug Evaluation and Research, FDA, Silver Spring, Maryland.
authors.forename: Haw-Jyh
authors.initials: HJ
authors.lastname: Chiu
authors.affiliation: Center for Drug Evaluation and Research, FDA, Silver Spring, Maryland.
authors.forename: Brenda J
authors.initials: BJ
authors.lastname: Gehrke
authors.affiliation: Center for Drug Evaluation and Research, FDA, Silver Spring, Maryland.
authors.forename: Candace
authors.initials: C
authors.lastname: Gomez-Broughton
authors.affiliation: Center for Drug Evaluation and Research, FDA, Silver Spring, Maryland.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Kane
authors.affiliation: Center for Drug Evaluation and Research, FDA, Silver Spring, Maryland.
authors.forename: Susan
authors.initials: S
authors.lastname: Kirshner
authors.affiliation: Center for Drug Evaluation and Research, FDA, Silver Spring, Maryland.
authors.forename: Nitin
authors.initials: N
authors.lastname: Mehrotra
authors.affiliation: Center for Drug Evaluation and Research, FDA, Silver Spring, Maryland.
authors.forename: Tiffany K
authors.initials: TK
authors.lastname: Ricks
authors.affiliation: Center for Drug Evaluation and Research, FDA, Silver Spring, Maryland.
authors.forename: Deborah
authors.initials: D
authors.lastname: Schmiel
authors.affiliation: Center for Drug Evaluation and Research, FDA, Silver Spring, Maryland.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Song
authors.affiliation: Center for Drug Evaluation and Research, FDA, Silver Spring, Maryland.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhao
authors.affiliation: Center for Drug Evaluation and Research, FDA, Silver Spring, Maryland.
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: Center for Drug Evaluation and Research, FDA, Silver Spring, Maryland.
authors.forename: Ann T
authors.initials: AT
authors.lastname: Farrell
authors.affiliation: Center for Drug Evaluation and Research, FDA, Silver Spring, Maryland.
authors.forename: Richard
authors.initials: R
authors.lastname: Pazdur
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D018033:Antibodies, Bispecific / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology*; D018941:Antigens, CD19 / Q000378:metabolism; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology*; D017252:CD3 Complex / Q000378:metabolism; D002986:Clinical Trials as Topic; D016207:Cytokines / Q000378:metabolism; D018572:Disease-Free Survival; D017277:Drug Approval; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D018365:Neoplasm, Residual; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000628:therapy; D012008:Recurrence; D012074:Remission Induction; D016896:Treatment Outcome; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D018033:Antibodies, Bispecific; D018941:Antigens, CD19; D000970:Antineoplastic Agents; D017252:CD3 Complex; D016207:Cytokines; C510808:blinatumomab