An Improved Benefit-Risk Profile of Duvelisib in Patients with Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma Who Received ≥2 Prior Therapies

Matthew Davids, Peter Hillmen, Marco Montillo, Julio Delgado, Bryone Kuss, Constantine Tam, Ulrich Jager, Paolo Ghia, Stephan Stilgenbauer, Florence Cymbalista, Stephanie Lustgarten, David Weaver, Hagop Youssoufian, Ian Flinn

Research output: Contribution to journalMeeting Abstractpeer-review

Abstract

Context
Despite effective frontline therapies, many patients with CLL or SLL eventually relapse and require additional therapies to control their disease. Duvelisib, 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.
Objective
To characterize the efficacy and safety of duvelisib in patients who had received ≥2 prior therapies in the phase 3 DUO trial.
Design
Patients were randomized 1:1 to oral duvelisib 25 mg BID or IV ofatumumab (OFA) 300 mg once, then 2000 mg for 12 doses total. The primary endpoint was progression-free survival (PFS) as assessed by a blinded IRC.
Results
Of the 319 total patients randomized, 191 had received ≥2 prior therapies (93 duvelisib; 98 ofatumumab). In this population, the median number of prior therapies was 3 (range, 2-10). Duvelisib was superior to OFA across all efficacy endpoints, including median PFS (duvelisib 16.4 mo, OFA 9.1 mo; HR, 0.4, P<0.0001), ORR (duvelisib 78.9%, OFA 38.6%; OR, 7.3, P<0.0001), and LNRR (duvelisib 88.4%, OFA 13.9%; P<0.0001). AEs occurring in >25% of patients who received duvelisib (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% and dose interruptions occurring in 74% of patients who received duvelisib; diarrhea/colitis (10%) and neutropenia (5%) were the most common AEs leading to dose reduction. 22 patients discontinued duvelisib 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 patient. 11 patients (12%) treated with duvelisib experienced a fatal AE. The only fatal events to occur in >1 patient were hemorrhagic stroke (n=2) and staphylococcal pneumonia (n=2). AEs with OFA were similar to those previously reported.
Conclusions
Duvelisib monotherapy had a manageable safety profile and demonstrated significantly improved clinical outcomes over OFA in CLL/SLL patients who had received ≥2 prior therapies, a population in need of additional targeted therapies.
Original languageEnglish
Article numberCLL-097
Pages (from-to)S276-S276
Number of pages1
JournalClinical Lymphoma, Myeloma & Leukemia
Volume19
Issue numberS1
DOIs
Publication statusPublished - Sep 2019
EventSociety of Hematologic Oncology 2019 Annual Meeting - Hilton Americas, Houston, United States
Duration: 11 Sep 201914 Sep 2019
https://www.soho2019.com/ (Conference website)

Keywords

  • Duvelisib
  • relapsed CLL/SLL
  • Progression-free survival
  • PI3K
  • CLL
  • chronic lymphocytic leukemia

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