FDA Approval: Ibrutinib for Patients with Previously Treated Mantle Cell Lymphoma and Previously Treated Chronic Lymphocytic Leukemia.
On November 13, 2013, the FDA granted accelerated approval to ibrutinib (IMBRUVICA capsules; Pharmacyclics, Inc.) for the treatment of patients with mantle cell lymphoma (MCL) who have received at least one prior therapy. On February 12, 2014, the FDA granted accelerated approval for the treatment of patients with chronic lymphocytic leukemia (CLL) who have received at least one prior therapy. Ibrutinib is a first-in-class Bruton's tyrosine kinase (BTK) inhibitor that received all four expedited programs of the FDA: Fast-Track designation, Breakthrough Therapy designation, Priority Review, and Accelerated Approval. Both approvals were based on overall response rate (ORR) and duration of response (DOR) in single-arm clinical trials in patients with prior treatment. In MCL (N = 111), the complete and partial response rates were 17.1% and 48.6%, respectively, for an ORR of 65.8% [95% confidence interval (CI), 56.2%-74.5%]. The median DOR was 17.5 months (95% CI, 15.8-not reached). In CLL (N = 48), the ORR was 58.3% (95% CI, 43.2%-72.4%), and the DOR ranged from 5.6 to 24.2 months. The most common adverse reactions (≥ 30% in either trial) were thrombocytopenia, diarrhea, neutropenia, bruising, upper respiratory tract infection, anemia, fatigue, musculoskeletal pain, peripheral edema, and nausea.
Office of Hematology and Oncology Products, Office of New Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland. romeo.declaro@fda.hhs.gov.
R Angelo
RA
de Claro
Office of Hematology and Oncology Products, Office of New Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
Karen M
KM
McGinn
Office of Hematology and Oncology Products, Office of New Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
Nicole
N
Verdun
Office of Hematology and Oncology Products, Office of New Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
Shwu-Luan
SL
Lee
Office of Hematology and Oncology Products, Office of New Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
Haw-Jyh
HJ
Chiu
Office of Hematology and Oncology Products, Office of New Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
Haleh
H
Saber
Office of Hematology and Oncology Products, Office of New Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
Margaret E
ME
Brower
Office of Hematology and Oncology Products, Office of New Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
C J George
CJ
Chang
Office of Clinical Pharmacology, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
Elimika
E
Pfuma
Office of Clinical Pharmacology, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
Bahru
B
Habtemariam
Office of Clinical Pharmacology, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
Julie
J
Bullock
Office of Biostatistics, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
Yun
Y
Wang
Office of Biostatistics, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
Lei
L
Nie
Office of New Drug Quality Assessment, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
Xiao-Hong
XH
Chen
Office of New Drug Quality Assessment, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
Donghao Robert
DR
Lu
Office of New Drug Quality Assessment, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
Ali
A
Al-Hakim
Office of Hematology and Oncology Products, Office of New Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
Robert C
RC
Kane
Office of Hematology and Oncology Products, Office of New Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
Edvardas
E
Kaminskas
Office of Hematology and Oncology Products, Office of New Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
Robert
R
Justice
Office of Hematology and Oncology Products, Office of New Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
Ann T
AT
Farrell
Office of Hematology and Oncology Products, Office of New Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
Richard
R
Pazdur
D000225:Adenine / Q000031:analogs & derivatives; D000368:Aged; D002986:Clinical Trials as Topic; D017277:Drug Approval / Q000331:legislation & jurisprudence; D005260:Female; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000473:pathology; D020522:Lymphoma, Mantle-Cell / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010880:Piperidines; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011720:Pyrazoles / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D011743:Pyrimidines / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D014481:United States
D010880:Piperidines; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011743:Pyrimidines; C551803:ibrutinib; D000225:Adenine