Phase 1b-2a trial of duvelisib plus romidepsin for relapsed or refractory T cell lymphomas

PI3K-δ inhibitors have shown impressive activity in lymphoid malignancies but have been hampered by toxicities, leading to market withdrawals. In a previous study, activity of the PI3K-δγ inhibitor duvelisib in T cell lymphomas was associated with inflammatory adverse events. A phase 1b-2a trial at Memorial Sloan Kettering Cancer Center (New York, NY) and Dana-Farber Cancer Institute (Boston, MA) evaluated addition of either romidepsin (HDAC inhibitor) or bortezomib (proteasome inhibitor) to duvelisib for relapsed or refractory T cell lymphoma (R/R TCL). The study showed that addition of romidepsin, but not bortezomib, to duvelisib appeared to increase efficacy while attenuating P13K inhibitor-driven toxicity. Duvelisib plus romidepsin resulted in less grade 3 or 4 hepatotoxicity (14% of patients) than was seen with duvelisib monotherapy in a previous study (40%). Overall and complete response rates with duvelisib plus romidepsin were 55% and 34%, respectively. Among patients with peripheral T cell lymphomas, ORR and CRR were 56% and 44%, respectively, with exploratory analyses showing increased response rates in patients with follicular helper T cell subtype. The authors conclude that combined PI3K and HDAC inhibition had promising efficacy among patients with R/R TCL.