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.
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 language | English |
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Article number | 165 |
Pages (from-to) | 213-214 |
Number of pages | 2 |
Journal | Hematological Oncology |
Volume | 37 |
Issue number | S2 |
DOIs | |
Publication status | Published - Jun 2019 |
Event | 15th International Conference on Malignant Lymphoma - Palazzo dei Congressi, Lugano, Switzerland Duration: 18 Jun 2019 → 22 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