Duvelisib demonstrated deep, durable responses and promising efficacy data across peripheral T-cell lymphoma subgroups.
The oral dual PI3K-δ and PI3K-γ inhibitor duvelisib (Copiktra) displayed promising efficacy, including deep and durable responses, in patients with relapsed or refractory peripheral T-cell lymphoma (PTCL), according to data from the phase 2 PRIMO trial (NCT03372057) published in Journal of Clinical Oncology.1
Findings showed that patients with PTCL who received duvelisib (n = 123) achieved an overall response rate (ORR) of 48% (95% CI, 39.1-56.8) per by independent review committee (IRC) assessment and a complete response (CR) rate of 33.3% (95% CI, 25-41.7). Moreover, patients experienced a median duration of response (DOR) of 7.9 months (95% CI, 6.4-21.0) and a median duration of CR of 7.9 months (95% CI, 6.4-22.7). Median progression-free survival (PFS) and overall survival (OS) among patients were 3.4 months (95% CI, 1.8-3.9) and 12.4 months (95% CI, 8.4-22.7), respectively.
“The PRIMO study confirms significant activity with duvelisib monotherapy in patients with relapsed or refractory PTCL,” lead study author Neha Mehta-Shah, MD, and coauthors wrote in the publication. “Based on the overall efficacy and safety profile demonstrated in the PRIMO study, duvelisib has been listed as a treatment option for relapsed or refractory PTCL within the National Comprehensive Cancer Network guidelines.”2
Mehta-Shah is an assistant professor of medicine at the Washington University School of Medicine in St. Louis, Missouri.
The open-label, multi-center trial enrolled patients who were at least 18 years of age with histologically confirmed PTCL. Patients were also required to have received at least 2 prior cycles of 1 standard PTCL treatment regimen and an ECOG performance status of 2 or less.1,3
If patients had primary leukemic PTCL subtypes, received prior PI3k inhibition or allogeneic stem cell transplants, central nervous system involvement, or transformed mycosis fungoides, they were not included in the trial.
In the dose-optimization phase of the trial, patients were randomly assigned to 2 cohorts where patients received either twice-daily, 25-mg oral doses of duvelisib (n = 20) or twice-daily, 75-mg oral doses of duvelisib (n = 13).1 Both cohorts in the dose-optimization phase of the trial had continuous 28-day cycles. In the dose-expansion phase of the trial, patients received twice-daily, 75-mg oral doses of duvelisib for 2 cycles, then those who achieved CR, partial response, or stable disease received twice-daily 25-mg oral doses of duvelisib (n = 123).
ORR per IRC assessment was the trial’s primary end point. Safety, DOR, PFS, OS, and disease control rate served as secondary end points for the trial. Additionally, progressive disease responses and biomarkers were exploratory end points.
Baseline characteristics revealed that patients had a median age of 65 years (range, 21-92) and were mostly White (74.8%) and male (54.5%). The median time from initial diagnosis among patients was 18.2 months (range, 0.2-195.5), whereas patients’ median time from most recent relapsed or refractory diagnosis was 1.15 months (range, 0-142.9). Baseline histology among patients broke down as not otherwise specified PTCL (43.1%), angioimmunoblastic T-cell lymphoma (AITL; 30.1%), anaplastic large-cell lymphoma (ALCL; 16.3%), and other (10.6%). Patients had a median of 2 prior lines of therapy (range, 1-9), with most patients having 3 or more prior lines of therapy (48%), 2 prior lines of therapy (23.6%), and 1 prior line of therapy (27.6%). Disease stages at screening for patients were I (4.1%), II (4.1%), III (33.3%), IV (57.7%), and missing (0.8%).
ORRs for AITL (n = 37), not otherwise specified PTCL (n = 53), and ALCL (n = 20) subgroups were 62.2% (95% CI, 46.5-77.8), 49.1% (95% CI, 35.6-62.5), and 15% (95% CI, 0-30.6), respectively. CR rates for the respective groups were 51.4% (95% CI, 35.2-67.5), 30.2% (95% CI, 17.8-42.5), and 15% (95% CI, 0-30.6). Each respective subgroup achieved a median PFS of 8.3 months (95% CI, 3.7-13.1), 3.4 months (95% CI, 1.8-4.4), and 1.6 (95% CI, 1.1-1.7), respectively, and a respective median OS of 18.1 months (95% CI, 9.6-not evaluable [NE]), 11 months (95% CI, 5.1-30.4), and 6.3 months (95% CI, 1.8-20.1),
Regarding safety, 97.6% of patients experienced any-grade treatment-emergent adverse effects (TEAEs), and 74% of patients experienced grade 3 or higher TEAEs. Common any-grade TEAEs that occurred in at least 15% of patients were increased alanine aminotransferase levels (37.4%), increased aspartate aminotransferase levels (35.8%), decreased neutrophil count (33.3%), diarrhea (33.3%), and fatigue (26%). Common grade 3 or higher TEAEs occurred in at lease 5% of patients were increased aspartate aminotransferase levels (17.1%), decreased neutrophil count (17.9%), decreased neutrophil count (17.9%), diarrhea (9.8%) and decreased platelet counts (8.9%)
