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

Purpose of the Study: 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‐, 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 duvelisib in patients who had received 2 prior therapies in the phase 3 DUO trial (NCT02004522).

Summarized Description of the Project: Patients were randomized 1:1 to oral duvelisib 25 mg BID or IV ofatumumab 300 mg once, then 2000 mg for 12 doses total. The primary endpoint was progression‐free survival (PFS) as assessed by a blinded independent review committee (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 ofatumumab across all efficacy endpoints (Table). 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% of patients 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 (23%) discontinued duvelisib due to a related AE; diarrhea/colitis (n=8), pneumonia (n=3), and pneumonitis (n=2) were the only treatment‐related events (as assessed by investigator) 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 pneumonia (n=3). AEs with ofatumumab were similar to those previously reported.

Conclusion: Duvelisib monotherapy had a manageable safety profile and demonstrated significantly improved clinical outcomes over ofatumumab in CLL/SLL patients who had received 2 prior therapies, a population in need of additional targeted therapies.