Management of adverse events associated with idelalisib treatment: expert panel opinion.
Idelalisib is a first-in-class selective, oral, phosphatidylinositol 3-kinase delta (PI3Kδ) inhibitor approved for the treatment of several types of blood cancer. Idelalisib has demonstrated significant efficacy and a tolerable safety profile in clinical trials. However, the US prescribing information contains a black box warning for fatal and/or severe diarrhea or colitis, hepatotoxicity, pneumonitis and intestinal perforation. An expert panel was convened to review the pathology of these treatment-emergent adverse events (TEAEs) to propose key management tools for patients receiving idelalisib therapy. This article provides an overview of idelalisib TEAEs reported in clinical trials, and a summary of the panel's recommendations for identification and management of idelalisib treatment-emergent diarrhea or colitis as well as a discussion of transaminitis and pneumonitis. For idelalisib-related diarrhea or colitis (including unresolved grade 2 and grade ≥ 3), after exclusion of infectious causes, the panel recommends individualized treatment with budesonide or oral or intravenous steroid therapy.
a Stanford Cancer Institute, Stanford University School of Medicine , Stanford , CA , USA.
Steven E
SE
Coutré
b Hofstra North Shore-LIJ School of Medicine , New Hyde Park , NY , USA.
Jacqueline C
JC
Barrientos
c CLL Center, Dana Farber Cancer Institute, Harvard School of Medicine , Boston , MA , USA.
Jennifer R
JR
Brown
d Department of Medicine Hematology/Oncology , David Geffen School of Medicine at UCLA , Santa Monica , CA , USA.
Sven
S
de Vos
e Weill Cornell Medical College , New York , NY , USA.
Richard R
RR
Furman
f UC Irvine Medical Center , Orange , CA , USA.
Michael J
MJ
Keating
g Gilead Sciences, Inc. , Seattle , WA , USA.
Daniel
D
Li
f UC Irvine Medical Center , Orange , CA , USA.
Susan M
SM
O'Brien
h Swedish Cancer Institute Hematologic Malignancies Program, Swedish Medical Group , Seattle , WA , USA.
John M
JM
Pagel
i Division of Gastroenterology, Duke University Medical Center , Durham , NC , USA.
Martin H
MH
Poleski
j Willamette Valley Cancer Institute, The US Oncology Network , Eugene , OR , USA.
Jeff P
JP
Sharman
k Gilead Sciences, Inc. , Foster City , CA , USA.
Nai-Shun
NS
Yao
l Medical Informatics, Department of Medicine , Memorial Sloan-Kettering Cancer Center , New York , NY , USA.
Andrew D
AD
Zelenetz
D000465:Algorithms; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D058543:Class Ia Phosphatidylinositol 3-Kinase / Q000378:metabolism; D004035:Diet Therapy; D019468:Disease Management; D064420:Drug-Related Side Effects and Adverse Reactions / Q000175:diagnosis* / Q000628:therapy*; D004791:Enzyme Inhibitors / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D019337:Hematologic Neoplasms / Q000150:complications / Q000188:drug therapy / Q000378:metabolism / Q000401:mortality; D006801:Humans; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011687:Purines / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D052999:Quinazolinones / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D058543:Class Ia Phosphatidylinositol 3-Kinase; D004791:Enzyme Inhibitors; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D011687:Purines; D052999:Quinazolinones; D058570:TOR Serine-Threonine Kinases; C552946:idelalisib
Idelalisib; colitis; diarrhea; phosphatidylinositol 3-kinase delta (PI3Kδ) inhibitor; pneumonitis; transaminitis