Retrospective Analysis of the Impact of Adverse Event–Triggered Idelalisib Interruption and Dose Reduction on Clinical Outcomes in Patients With Relapsed/Refractory B-Cell Malignancies

Shuo Ma*, Rebecca J. Chan, Lin Gu, Guan Xing, Nishanthan Rajakumaraswamy, Bianca B. Ruzicka, Nina D. Wagner-Johnston

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Idelalisib is a phosphatidylinositol 3-kinase δ inhibitor approved for relapsed/refractory follicular lymphoma, a type of indolent non-Hodgkin lymphoma (iNHL), and chronic lymphocytic leukemia (CLL). Idelalisib-triggered adverse events (AEs) may be managed with treatment interruption and/or dose reduction, potentially extending therapy duration and increasing the likelihood of continued response. Patients and Methods: Post hoc analyses were conducted to evaluate clinical outcomes after AE-induced idelalisib interruption for 125 patients with iNHL and 283 with CLL. Results: Progression-free survival (PFS) was longer for patients with iNHL who experienced ≥ 2 interruptions versus those with 0 interruptions who discontinued idelalisib or study because of AEs (hazard ratio 0.33; P =.0212). Both PFS and overall survival were longer for patients with CLL with ≥ 2 interruptions versus 0 interruptions in those who discontinued therapy because of an AE (hazard ratio PFS 0.50, overall survival 0.41; P <.005). Clinical benefits persisted for patients with CLL who experienced treatment interruption after receiving idelalisib for ≥ 6 months. Supplementing interruption with dose reduction did not worsen clinical outcomes. However, time off therapy of ≥ 8% may diminish the clinical benefit of treatment interruption. Conclusion: Idelalisib interruption and dose reduction were associated with enhanced clinical outcomes for patients with relapsed/refractory iNHL or CLL who experienced an AE, supporting this management strategy when indicated.

Original languageEnglish (US)
JournalClinical Lymphoma, Myeloma and Leukemia
DOIs
StateAccepted/In press - 2021

Keywords

  • Alternative dosing regimen
  • Chronic lymphocytic leukemia
  • Follicular lymphoma
  • PI3K inhibitor
  • Toxicity management

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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