medwireNews: The oral, dual inhibitor of phosphoinositide 3-kinase (PI3K)-δ and –γ duvelisib significantly delays disease progression or death compared with ofatumumab in patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), data from the DUO trial show.
Therefore, “[d]uvelisib’s efficacy and manageable safety profile support its consideration as a novel, oral monotherapy for [relapsed or refractory] CLL/SLL patients,” say Ian Flinn (Sarah Cannon Research Institute, Nashville, Tennessee, USA) and co-authors.
For the phase III trial, 319 patients (median age 69 years, 60% men) with relapsed or refractory CLL/SLL were randomly assign to receive oral duvelisib 25 mg twice daily (n=160) or to receive the humanized anti-CD20 antibody ofatumumab given intravenously according to the approved monotherapy dosing schedule for CLL (n=159).
After a median follow-up of 22.4 months, Flinn and team found that patients in the duvelisib group had a significant 48% lower risk for disease progression or death than those in the ofatumumab group, with median profession-free survival (PFS) at 13.3 months and 9.9 months, respectively.
The estimated PFS rates at 6 and 12 months were 78% and 60%, respectively, in the duvelisib arm, and 72% and 39%, respectively, in the ofatumumab arm.
The researchers note that PFS was significantly higher with duvelisib than with ofatumumab in all of the subgroups they examined, including patients with high-risk chromosome 17p13.1 deletions and/or TP53 mutations. For this group, duvelisib was associated with a 60% reduced risk for disease progression or death versus ofatumumab, with median PFS at 12.7 months versus 9.0 months.
The overall response rate (ORR) was also significantly higher with duvelisib than with ofatumumab (73.8 vs 45.3%), but there was no difference in overall survival, which was estimated to be 86.0% at 12 months in both treatment groups.
However, this “may be explained by the availability of multiple CLL therapies to rescue patients on either arm following disease progression,” Flinn et al remark.
Adverse events (AEs) of grade 3 or higher occurred more often with duvelisib than with ofatumumab (87 vs 48%), but the investigators point out that the median treatment period was more than twice as long for duvelisib as for ofatumumab (median exposure, 50 versus 23 weeks).
The most common severe AEs reported in the duvelisib arm were neutropenia (30%), diarrhea (15%), pneumonia (14%), anemia (13%), and colitis (12%), compared with neutropenia (17%) and anemia (5%) in the ofatumumab arm.
There were four treatment-related deaths in the duvelisib group and none in the ofatumumab group.
The study findings are published in Blood.
By Laura Cowen
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