An improved benefit-risk profile of duvelisib in patients with chronic lymphocytic leukemia or small lymphocytic lymphoma who received 2 or more prior therapies

I. W. Flinn, M. S. Davids, P. Hillmen, M. Montillo, J. Delgado, B. J. Kuss, C. S. Tam, U. Jager, P. Ghia, S. Stilgenbauer, S. Lustgarten, D. T. Weaver, H. Youssoufian, F. Cymbalista

    Research output: Contribution to journalMeeting Abstractpeer-review

    Abstract

    Introduction: Despite effective frontline therapies, many patients (pts) with CLL or SLL eventually relapse and require additional therapies to control their disease. Duvelisib (DUV), a first-in-class oral dual PI3K-δ,γ inhibitor, was approved by the FDA for the treatment of relapsed or refractory CLL or SLL after ≥2 prior therapies. Here we present the efficacy and safety of DUV in pts who had received ≥2 prior therapies in the phase 3 DUO trial (NCT02004522).

    Methods: Pts were randomized 1:1 to oral DUV 25 mg BID or IV ofatumumab (OFA) 300 mg once, then 2000 mg for 12 doses total. The primary endpoint was PFS as assessed by a blinded IRC.

    Results: Of the 319 total pts randomized, 191 had received ≥2 prior therapies (93 DUV; 98 OFA). In this population, the median number of prior therapies was 3 (range, 2-10). DUV was superior to OFA across all efficacy endpoints (Table). AEs occurring in >25% of pts who received DUV (all grade; grade ≥3) were diarrhea/colitis (58%; 24%), neutropenia (40%; 38%), pyrexia (33%; 2%), upper respiratory infection (30%; 0%), pneumonia (29%; 22%), and fatigue (26%; 3%). Many AEs were successfully managed through dose modifications, with dose reductions occurring in 28% of pts and dose interruptions occurring in 74% of pts who received DUV; diarrhea/colitis (10%) and neutropenia (5%) were the most common AEs leading to dose reduction. 22 pts (23%) discontinued DUV due to a related AE; diarrhea/colitis (n = 8), pneumonia (n = 3), and pneumonitis (n = 2) were the only treatment-related events leading to discontinuation in >1 pt. 11 pts (12%) treated with DUV experienced a fatal AE. The only fatal events to occur in >1 pt were hemorrhagic stroke (n = 2) and staphylococcal pneumonia (n = 2). AEs with OFA were similar to those previously reported.

    Conclusions: DUV monotherapy had a manageable safety profile and demonstrated significantly improved clinical outcomes over OFA in CLL/SLL pts who had received ≥2 prior therapies, a population in need of additional targeted therapies.
    Original languageEnglish
    Article number165
    Pages (from-to)213-214
    Number of pages2
    JournalHematological Oncology
    Volume37
    Issue numberS2
    DOIs
    Publication statusPublished - Jun 2019
    Event15th International Conference on Malignant Lymphoma - Palazzo dei Congressi, Lugano, Switzerland
    Duration: 18 Jun 201922 Jun 2019
    https://www.icml.ch/icml/home.html (Organisation's website, with links to past conferences)

    Keywords

    • chronic lymphocytic leukemia (CLL)
    • Duvelisib
    • P13K/AKT/mTOR

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