Efficacy and tolerability of duvelisib in relapsed/refractory peripheral T-cell lymphoma: A multicenter real-world analysis.

7067 Background: Relapsed/refractory (R/R) peripheral T-cell lymphomas (PTCL) are a rare group of non-Hodgkin lymphomas with median survival at relapse of 6-10 months and few treatment options. Duvelisib is a g/∆ phosphatidylinositol 3-kinase inhibitor approved in CLL and NCCN compendium listed in PTCL. In indolent lymphomas, concerns for cumulative duvelisib toxicity limit its use. In contrast, studies in R/R PTCL show duvelisib to be well-tolerated. Therefore, we sought to assess the efficacy and tolerability of duvelisib in a real world setting in R/R PTCL. Methods: We conducted a retrospective analysis of patients with R/R PTCL treated with duvelisib from 2012-2025 at 12 centers. Results: We identified 207 patients with PTCL: nodal PTCL with TFH phenotype (n=106, 51%), PTCL-NOS (n=78, 38%), ALCL (n=16, 8%), enteropathy associated T-cell lymphoma (n=4, 2%), NK/T-cell lymphoma (n=2, 1%), adult T-cell leukemia/lymphoma (n=1, 0.5%). 90 patients (43%) were female. Median age was 64; median International Prognostic Index score 3. Median prior lines of therapy was 2 (range 1-9). 26% received frontline transplant (23% auto, 3% allo). 118 patients received single agent duvelisib; 89 patients received duvelisib in combination with other agents (66 romidepsin, 12 bortezomib, 4 azacitadine, 3 ruxolitinib, 4 other). Of patients with response data, ORR was 51% (94/186; 31% CR, 17% PR) with median OS 12 months. ORR in patients with TFH-phenotype vs. non-TFH phenotype was 60% and 41% respectively. ORR in patients treated with single agent duvelisib and duvelisib combinations was 46% (46/99; 29% CR, 17% PR) and 55% (48/87; 39% CR, 16% PR), respectively with no difference in OS. Median duration of therapy was 84 days; the most common reason for discontinuation was progression (41%, 76/186). 13% (25/196) underwent allo-SCT after duvelisib therapy. Toxicity data is summarized in our table. In patients receiving single agent duvelisib therapy, rates of cytopenia were lower (7% vs. 34%, p<0.001) and rates of colitis were higher (17% vs. 7%, p= 0.03). Conclusions: In this real world, multicenter analysis of patients with R/R PTCL treated with duvelisib-based regimens, the ORR of 51% was consistent with published trials. Duvelisib therapy was well tolerated and a minority required hospitalization for toxicity. This suggests that duvelisib is safe in patients with R/R PTCL who have poor prognosis and limited treatment options. Adverse Event Full Cohortn (%)n=207 Single agent n (%)n=118 Combination therapyn (%)n=89 Single vs. Combination p value SteroidGivenn (% full cohort) Hospitalizationn (% full cohort) Rash 41 (20%) 24 (20%) 17 (19%) 0.83 23 (11%) 6 (3%) Colitis 26 (13%) 20 (17%) 6 (7%) 0.03 20 (10%) 16 (8%) Pneumonitis 7 (3%) 4 (3%) 3 (3%) 0.99 5 (2%) 3 (1%) Cytopenia 38(18%) 8 (7%) 30 (34%) <0.001 * * Transaminitis 33 (16%) 21 (18%) 12 (13%) 0.40 * * Infection 66 (32%) 36 (31%) 30 (34%) 0.63 N/A 42 (20%) *Not available.