Abstract
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.
Keywords:
Idelalisib; colitis; diarrhea; phosphatidylinositol 3-kinase delta (PI3Kδ) inhibitor; pneumonitis; transaminitis.
Publication types
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Algorithms
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Antineoplastic Agents / adverse effects*
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Antineoplastic Agents / pharmacology
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Antineoplastic Agents / therapeutic use
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Class Ia Phosphatidylinositol 3-Kinase / metabolism
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Diet Therapy
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Disease Management
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Drug-Related Side Effects and Adverse Reactions / diagnosis*
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Drug-Related Side Effects and Adverse Reactions / therapy*
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Enzyme Inhibitors / adverse effects*
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Enzyme Inhibitors / pharmacology
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Enzyme Inhibitors / therapeutic use
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Hematologic Neoplasms / complications
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Hematologic Neoplasms / drug therapy
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Hematologic Neoplasms / metabolism
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Hematologic Neoplasms / mortality
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Humans
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Phosphatidylinositol 3-Kinases / metabolism
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Phosphoinositide-3 Kinase Inhibitors
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Proto-Oncogene Proteins c-akt / metabolism
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Purines / adverse effects*
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Purines / pharmacology
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Purines / therapeutic use
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Quinazolinones / adverse effects*
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Quinazolinones / pharmacology
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Quinazolinones / therapeutic use
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Signal Transduction / drug effects
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TOR Serine-Threonine Kinases / metabolism
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Treatment Outcome
Substances
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Antineoplastic Agents
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Enzyme Inhibitors
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Phosphoinositide-3 Kinase Inhibitors
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Purines
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Quinazolinones
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Class Ia Phosphatidylinositol 3-Kinase
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Proto-Oncogene Proteins c-akt
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TOR Serine-Threonine Kinases
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idelalisib