Idelalisib immune-related toxicity is associated with improved treatment response

Leuk Lymphoma. 2021 Dec;62(12):2915-2920. doi: 10.1080/10428194.2021.1948038. Epub 2021 Jul 28.

Abstract

Idelalisib is associated with increased occurrence of immune-related adverse events (irAEs). Clinical observations suggest a correlation between immune checkpoint inhibitor-induced irAEs and survival outcomes in patients with solid tumors; however, this relationship in hematologic malignancies is not well understood. In a post hoc analysis of 3 registrational trials, we explored the relationship between Grade ≥3 diarrhea/colitis and alanine/aspartate transaminase (ALT/AST) elevation incidences and efficacy endpoints in patients with indolent non-Hodgkin lymphoma (iNHL), follicular lymphoma (FL), and chronic lymphocytic leukemia treated with idelalisib. Grade ≥3 diarrhea/colitis was associated with higher overall response rate (ORR) and longer progression-free survival (PFS) for all subgroups. Grade ≥3 ALT/AST elevations were associated with improved duration of response and overall survival for all subgroups and improved ORR and PFS for patients with FL or iNHL. Our analysis in hematologic malignancies showed a trend correlating idelalisib-induced Grade ≥3 irAEs with improved efficacy.

Keywords: Idelalisib; PI3K inhibitor; chronic lymphocytic leukemia; follicular lymphoma; immune-related adverse event; indolent non-Hodgkin lymphoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Colitis* / chemically induced
  • Colitis* / drug therapy
  • Diarrhea / chemically induced
  • Hematologic Neoplasms* / drug therapy
  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell* / drug therapy
  • Leukemia, Lymphocytic, Chronic, B-Cell* / pathology
  • Lymphoma, Follicular* / drug therapy
  • Lymphoma, Non-Hodgkin* / pathology
  • Purines
  • Quinazolinones / adverse effects

Substances

  • Purines
  • Quinazolinones
  • idelalisib