Duvelisib (Copiktra) in combination with nivolumab (Opdivo) yielded responses in patients with relapsed/refractory cutaneous T-cell lymphoma (CTCL), although immune-mediated adverse effects (imAEs) limited the ability to dose patients, according to data from a phase 1 trial (NCT04652960) presented at the
Findings showed that evaluable patients (n = 19) achieved an overall response rate (ORR) of 26%. Responses occurred exclusively in patients with mycosis fungoides (MF; n = 14), who experienced an ORR of 36%; no responses were observed among the patients with Sézary syndrome (SS; n = 5). The 5 responses comprised 1 complete response (CR) and 4 partial responses (PR), and the median duration of response was 20.2 weeks. One patient remained in an ongoing PR at 97 weeks, and 1 patient achieved a CR with a duration of response of 125 weeks.
Dose-limiting toxicities (DLTs) were observed across dose levels and consisted predominantly of transaminitis, including grade 3 and grade 4 events; additional DLTs included grade 4 Stevens-Johnson syndrome, grade 3 Pseudomonas infection, and grade 3 pancreatitis.
“The response rate of duvelisib plus nivolumab led to some durable remission, but similar [with] what I would say we could see with PD-1 inhibitors alone. The [imAEs] were significant. We would not recommend this combination in patients who have cutaneous T-cell lymphoma, and further studies of this combination would really have to account for immune-mediated toxicities to mitigate that [risk],” lead study author Neha Mehta-Shah, MD, MSCI, an associate professor of medicine in the Division of Oncology at Washington University School of Medicine in St. Louis, Missouri, said in a presentation of the data.
The phase 1 trial enrolled patients at least 18 years of age with stage IIB to IVB MF or SS who had measurable disease per the Global Cutaneous Lymphoma Response Criteria and had received at least 1 prior line of systemic therapy.1,2 Eligible patients had an ECOG performance status of 2 or less, New York Heart Association functional class 2B or better, and adequate hematologic and end-organ function.
Duvelisib was administered twice daily in combination with nivolumab and was evaluated across 2 dosing schedules. Patients initially received duvelisib continuously on days 1 to 28 at dose levels of 25 mg, 50 mg, and 75 mg twice daily; after DLTs emerged, an intermittent schedule of duvelisib on days 1 to 14 was evaluated at the same dose levels.
The primary end points were to determine the recommended phase 2 dose or maximum tolerated dose and the ORR at 4 months.
Among 19 patients enrolled, the median age was 66 years (range, 38-75), and 53% were male. The most common disease stage was IVA (53%), followed by IIB (26%). Patients had received a median of 5 prior therapies (range, 1-22), and the median time from diagnosis to study treatment was 30 months (range, 6-256).
Recurrent toxicities included grade 3 or higher transaminitis in 58% of patients (11/19) and rash in 43% (8/19); no patient experienced grade 3 or higher diarrhea.
Reported grade 3 AEs included transaminitis (28%), rash/erythroderma (11%), and fatigue (6%), and grade 4 AEs included transaminitis (17%) and Stevens-Johnson syndrome (6%). Grade 3 infections occurred in 22% of patients, including sepsis (11%), skin infection (6%), CMV reactivation (6%), and osteomyelitis (6%).
Eleven patients discontinued therapy because of an AE, with the most common being transaminitis (n = 6). One patient each discontinued treatment due to pneumonitis, sepsis, Stevens-Johnson syndrome, Pseudomonas infection, and pancreatitis. An additional 4 patients discontinued because of disease progression, and 3 discontinued because of patient withdrawal. Among patients who discontinued for toxicity, the median time to next treatment was 8 weeks (range, 0-125).
