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Duvelisib monotherapy demonstrated encouraging efficacy for patients with relapsed/refractory peripheral T-cell lymphoma.
Duvelisib (Copiktra) monotherapy demonstrated encouraging efficacy for patients with relapsed/refractory peripheral T-cell lymphoma (PTCL), according to updated dose-expansion results of the phase 2 PRIMO trial (NCT03372057) that were presented at the 2021 Pan Pacific Lymphoma Conference.1
At a median follow-up of 4 months, data showed that an independent review committee (IRC) recorded 20 (52.6%) responses, including 13 (34.2%) complete responses (CRs) in the 38-patient cohort. The median time to response was 55 days (29-114) and the median duration of response (DOR) was 233 days (range, 1+ to 334+).
Jasmin M. Zain, MD, director of the T-Cell Lymphoma Program and an associate clinical professor at City of Hope, presented the data from PRIMO, adding that duvelisib could be used as a bridge to transplant in this patient population.
“Monotherapy with duvelisib is a promising therapy for patients with relapsed/refractory PTCL, with ORR noted to be 50% with a complete response rate of 34% in the dose-expansion phase,” said Zain in presenting the findings.
She added that there is a clear medical need for new treatment options for the relapsed/refractory PTCL population.
“Patients with relapsed/refractory PTCL have a terrible prognosis with a median overall survival of less than 6 months,” she said. “Most approved therapies are associated with an overall response rate [ORR] of less than 30% and a median progression-free survival [PFS] of less than 4 months.
Duvelisib is an oral, dual inhibitor of phosphatidylinositol 3-kinase δ and γ (PI3K-δ,γ) that is currently approved relapsed/refractory chronic lymphocytic leukemia or small lymphocytic lymphoma after at least 2 prior therapies, as well as relapsed/refractory follicular lymphoma after at least 2 prior systemic therapies.
In PRIMO, investigators are evaluating the efficacy of single-agent duvelisib at 75 mg twice daily in approximately 120 patients with relapsed/refractory PTCL in the trial’s dose-expansion phase. Patients must have the following: PTCL with PTCL-not otherwise specified (55.3%), AITCL (26.3%), ALCL (18.4%), or NKTL (0%); measurable disease per International Working Group for PTCL; no transformation to aggressive lymphoma; no prior history of allogeneic stem cell transplant or treatment with PI3K inhibitor; and an ECOG performance status of 0 to 2.
In the PRIMO dose-optimization cohort, 33 patients were treated with 25 mg (n = 20) or 75 mg (n = 13) twice daily. The investigator-assessed objective response rate (ORR) at the 75-mg dose was 54%, the CR rate was 31%, and the median DOR was 12.2 months.2 The ICR-based ORR was 62% and the CR rate was not available. Based on these initial results, the researchers next treated patients in the dose-expansion phase with 75 mg of twice-daily duvelisib for 2 cycles to achieve tumor control, then with 25 mg of twice-daily duvelisib to maintain long-term disease control.
The primary end point is IRC-assessed ORR; secondary end points are safety, DOR, progression-free survival, disease control rate, and overall survival. Pharmacokinetic and pharmacodynamic markers are exploratory end points.
This dose-expansion phase included 38 patients. Women made up half the cohort and 73.7% of patients were White. The median time from initial diagnosis was 20 months (range, 6-196), and the median time from most recent relapsed/refractory diagnosis was 1.3 months (range, 0-143).
Investigators said the AE profile was consistent with previous PRIMO results. Overall, 32 patients (84%) discontinued treatment, half of which were due to disease progression (50%). Seven (18%) discontinued because of adverse events (AEs). Six (16%) patients remain on treatment.
Increased alanine aminotransferase (26%) and increased aspartate aminotransferase (24%) were the most common grade 3 or higher AEs. The only grade 3 or higher AE to appear in more than 5% of patients were decreased lymphocyte count (11%), rash (11%), and decreased neutrophil count (8%).
In June 2021, the European Medicines Agency granted marketing authorization for duvelisib monotherapy in patients with relapsed/refractory CLL who have previously received at least 2 therapies or those with follicular lymphoma whose disease is refractory to at least 2 previous systemic treatments.3
The decision was based on findings from the phase 3 DUO trial (NCT02004522), in which duvelisib reduced the risk of disease progression or death by 48% vs ofatumumab (Arzerra) in patients with relapsed/refractory CLL or SLL per IRC assessment.4 The median PFS in the investigative arm was 13.3 months (95% CI, 12.1-16.8) per IRC assessment vs 9.9 months (95% CI, 9.2-11.3) in the control arm (HR, 0.52; P <.0001).