R/R PTCL patients require novel, lineage-specific therapies with manageable toxicity to bridge them to HSCT. A prior phase I/II study of duvelisib/romidepsin(D/R) reported ORR of 58% and CRR of 42% with reduced grade 3-4 transaminitis(14%) vs duv-monotherapy. We report real-world outcomes on a multicenter cohort of 33 patients with R/R PTCL treated with D/R('21-'24).
The median age at diagnosis was 61.7y, with histological subtypes including nTFH(n=14), PTCL-NOS(n=10), CTCL(n=3), ENKTCL(n=1), ALK- ALCL(n=1), ATLL(n=1), and HSTCL(n=1). Median prior therapies were 1(range, 1-8); 12 patients relapsed and 21 were refractory to prior treatment. 7 had prior HSCT(6 auto, 1 allo). On D/R, patients received a median of 3.5 cycles(range, 2-19) with a median duration of 3.2m(range, 1.2-22.1). Among 33 evaluable lines of therapy, ORR and CRR were 52% and 45% respectively, with higher ORR(67 vs 39%) and CRR(60 vs 33%) in nTFH compared to non-nTFH. Median PFS and OS(HSCT-censored) were 23.4m and 15.6m (p=0.054, HR 0.36) for nTFH and 3.3m and 8.3m(p=0.1, HR 0.36) for non-nTFH patients. In 18 patients achieving CR/PR to D/R, median time to response was 2.3m(range, 0.7-5.6) and median DoR was 21.1m(range, 0.1-34.5). Post D/R, 12 patients bridged to allo-HSCT, and 3 received subsequent treatment before allo-HSCT.
Treatment was well tolerated, with grade 3-4 toxicities including ALT-transaminitis(n=6), AST-transaminitis(n=6), anemia(n=4), neutropenia(n=11), thrombocytopenia(n=6), febrile neutropenia(n=2), lymphopenia(n=14), leukocytosis(n=7), diarrhea(n=1), fatigue(n=5), rash(n=6) in 32 evaluable lines of therapy. Treatment-adverse events seldom led to discontinuation(n=2) and death(n=1). These findings reinforce D/R's efficacy and role as a bridge to curative HSCT in high-risk R/R PTCL.
