Detection of cases of progressive multifocal leukoencephalopathy associated with new biologicals and targeted cancer therapies from the FDA's adverse event reporting system.
OBJECTIVE
To identify and summarize FDA's Adverse Event Reporting System (FAERS) cases of progressive multifocal leukoencephalopathy (PML) associated with biological and targeted cancer therapies (BTCT) that were approved between 2009 and 2015.


METHODS
FAERS was searched using each BTCT name as primary or secondary suspect drug and the adverse reaction of PML. Among BTCTs with >2 case reports of PML, proportional reporting ratios (PRR) and 95% confidence intervals (CI) were calculated.


RESULTS
Among 49 new BTCTs, 82 cases of PML were found for 16 drugs. Significant PRR signals were found among 7 (14.6%) BTCTs including: brentuximab (24.5, CI:14.8-40.6), ofatumumab (16.3, CI:9.6-27.4), alemtuzumab (9.9, CI:6.0-16.4), obinutuzumab (7.4, CI:2.4-22.8), ibrutinib (5.6 CI:3.0-10.5), belimumab (4.5 CI:2.3-9.0), and idelalisib (4.1, CI:1.3-12.6). Among the 82 cases with significant signals, confirmation of the diagnosis of PML using objective criteria was found in 56% of the cases. A limitation of FAERS data is that missing data are common.


CONCLUSIONS
When using BTCTs, clinicians and patients consider the risk of PML versus the therapeutic benefit, particularly when used in combination with other drugs which may cause PML, such as rituximab. It is important to recognize that PML may occur in some conditions, such as chronic lymphocytic leukemia, regardless of drug therapy.
a College of Pharmacy , University of New Mexico , Albuquerque , NM , USA.
Dennis W
DW
Raisch
a College of Pharmacy , University of New Mexico , Albuquerque , NM , USA.
John A
JA
Rafi
a College of Pharmacy , University of New Mexico , Albuquerque , NM , USA.
Cheng
C
Chen
b College of Pharmacy , Medical University of South Carolina , Charleston , SC , USA.
Charles L
CL
Bennett
D000328:Adult; D016907:Adverse Drug Reaction Reporting Systems; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D001688:Biological Products / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D006801:Humans; D007968:Leukoencephalopathy, Progressive Multifocal / Q000139:chemically induced* / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy; D014481:United States; D014486:United States Food and Drug Administration
D000970:Antineoplastic Agents; D001688:Biological Products
FDA’s adverse event reporting system; Progressive multifocal leukoencephalopathy; biological drugs; data mining signal detection; targeted cancer therapies