title: 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.affiliation: *Department of Pathology and Laboratory Medicine †Division of Hematology and Medical Oncology, Weill Cornell Medical College, New York, NY.
authors.forename: Anna-Sophie
authors.initials: AS
authors.lastname: Weidner
authors.forename: Nicole C
authors.initials: NC
authors.lastname: Panarelli
authors.forename: Julia T
authors.initials: JT
authors.lastname: Geyer
authors.forename: Erica B
authors.initials: EB
authors.lastname: Bhavsar
authors.forename: Richard R
authors.initials: RR
authors.lastname: Furman
authors.forename: John P
authors.initials: JP
authors.lastname: Leonard
authors.forename: Jose
authors.initials: J
authors.lastname: Jessurun
authors.forename: Rhonda K
authors.initials: RK
authors.lastname: Yantiss
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects*; D017209:Apoptosis / Q000187:drug effects; D015415:Biomarkers / Q000032:analysis; D001706:Biopsy; D058534:Class I Phosphatidylinositol 3-Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D003106:Colon / Q000737:chemistry / Q000187:drug effects / Q000473:pathology*; D003113:Colonoscopy; D003967:Diarrhea / Q000139:chemically induced; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000737:chemistry / Q000187:drug effects / Q000473:pathology*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000201:enzymology; D008218:Lymphocytosis / Q000139:chemically induced; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D047428:Protein Kinase Inhibitors / Q000009:adverse effects*; D011687:Purines / Q000009:adverse effects*; D052999:Quinazolinones / Q000009:adverse effects*; D012008:Recurrence; D012189:Retrospective Studies; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D000305:Adrenal Cortex Hormones; D000970:Antineoplastic Agents; D015415:Biomarkers; D047428:Protein Kinase Inhibitors; D011687:Purines; D052999:Quinazolinones; D058534:Class I Phosphatidylinositol 3-Kinases; C486018:PIK3CD protein, human; C552946:idelalisib