Idelalisib-associated Colitis: Histologic Findings in 14 Patients.

Abstract

Idelalisib is an inhibitor of the PI3Kδ isoform approved for treatment of patients with relapsed chronic lymphocytic leukemia and indolent non-Hodgkin lymphoma. Many patients develop gastrointestinal symptoms during idelalisib therapy; however, the pathologic effects of this drug have not been characterized. We identified 50 patients who received at least 3 months of idelalisib therapy. Clinical findings and symptoms were noted for each patient, and endoscopic findings were recorded for those who underwent colonoscopic examination. Hematoxylin and eosin-stained sections from colonic biopsy samples were evaluated for histologic patterns of injury. Twenty-three (46%) patients experienced diarrhea during treatment with idelalisib, including 8 with severe symptoms (≥7 stools/d above baseline and/or requiring hospitalization). Fourteen patients underwent colonoscopic examination with mucosal biopsy. Twelve (86%) of these had colitis characterized by intraepithelial lymphocytosis, crypt cell apoptosis, and neutrophilic infiltration of crypt epithelium. Eleven patients had symptoms severe enough to warrant drug withdrawal, including 9 who were also treated with corticosteroids. Idelalisib commonly causes diarrheal symptoms in patients undergoing therapy for B-cell neoplasia, which may be severe in nearly 20% of patients. Characteristic histologic features include the combination of intraepithelial lymphocytosis and crypt cell apoptosis, often accompanied by neutrophils. Discontinuation of the drug results in symptomatic improvement and resolution of histologic changes.

• Authors: Anna-Sophie Weidner, Nicole C Panarelli, Julia T Geyer, Erica B Bhavsar, Richard R Furman, John P Leonard, Jose Jessurun, Rhonda K Yantiss
• Journal: The American journal of surgical pathology (Am J Surg Pathol) Vol. 39 Issue 12 Pg. 1661-7 (Dec 2015) ISSN: 1532-0979 [Electronic] United States
• PMID: 26448188 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adrenal Cortex Hormones
• Antineoplastic Agents
• Biomarkers
• Protein Kinase Inhibitors
• Purines
• Quinazolinones
• Class I Phosphatidylinositol 3-Kinases
• PIK3CD protein, human
• idelalisib

Topics

• Adrenal Cortex Hormones (therapeutic use)
• Aged
• Aged, 80 and over
• Antineoplastic Agents (adverse effects)
• Apoptosis (drug effects)
• Biomarkers (analysis)
• Biopsy
• Class I Phosphatidylinositol 3-Kinases (antagonists & inhibitors, metabolism)
• Colitis (chemically induced, drug therapy, metabolism, pathology)
• Colon (chemistry, drug effects, pathology)
• Colonoscopy
• Diarrhea (chemically induced)
• Female
• Humans
• Immunohistochemistry
• Intestinal Mucosa (chemistry, drug effects, pathology)
• Leukemia, Lymphocytic, Chronic, B-Cell (drug therapy, enzymology)
• Lymphocytosis (chemically induced)
• Lymphoma, Non-Hodgkin (drug therapy, enzymology)
• Male
• Middle Aged
• Molecular Targeted Therapy
• Protein Kinase Inhibitors (adverse effects)
• Purines (adverse effects)
• Quinazolinones (adverse effects)
• Recurrence
• Retrospective Studies
• Severity of Illness Index
• Treatment Outcome