Real-world Evidence of Duvelisib and Romidepsin in Relapsed/Refractory Peripheral and Cutaneous T-cell Lymphomas Open Access

• Duvelisib and romidepsin combination in real-world confirms efficacy, tolerability and safety for patients with R/R PTCL.

• Duvelisib and romidepsin combination offers a novel strategy to bridge eligible patients with R/R PTCL to allogeneic transplantation.

Patients with R/R PTCL require lineage-specific therapies to bridge them to HSCT. A prior phase I/II study of duvelisib/romidepsin (duv/romi) reported ORR of 58% and CRR of 42% with reduced grade 3-4 transaminitis (14%). We report real-world outcomes on a multicenter cohort of 38 patients with R/R PTCL treated with duv/romi. The median age at diagnosis was 64y, with histological subtypes including nTFH (n=17), PTCL-NOS (n=14), CTCL (n=3), ENKTCL (n=1), ALK- ALCL (n=1), ATLL (n=1), and HSTCL (n=1). Median prior therapies were 1 (IQR, 1-2); 15 patients relapsed and 23 were refractory to prior treatment with 8 having prior HSCT (5 auto, 3 allo). Patients received a median of 3 cycles (IQR, 2-4). Among 38 evaluable patients, ORR and CRR were 61% and 47%, respectively, with higher ORR (82% vs 43%) and CRR (71% vs 29%) in nTFH compared to non-nTFH. Median PFS and OS (HSCT-censored) were 11m (HR 0.31, 95%CI: 0.11-0.87; p=0.03) and 16m (HR 0.66, 95%CI: 0.23-1.87; p=0.4) for nTFH versus 3.3m and 8.3m for non-nTFH patients. The median TTR was 1.9m (IQR, 1.7-2.6), DoR was 21m (95%CI, 11-NR) and TTNT was 17m (95%CI, 6.4-NR). Post duv/romi, 11 patients were immediately bridged to allo-HSCT. Treatment was well tolerated, with most common grade 3-4 toxicities being lymphopenia (n=15), neutropenia (n=15), thrombocytopenia (n=10), ALT/AST-transaminitis (n=6), among others. Treatment-related adverse events seldom led to discontinuation (n=4) and death (n=1). These findings reinforce duv/romi's efficacy and role as a bridge to curative HSCT in high-risk R/R PTCL.