Romidepsin + CHOP

Romidepsin + CHOP (also known as Ro-CHOP) is a combination therapy investigated for previously untreated peripheral T-cell lymphoma (PTCL). Romidepsin is a histone deacetylase inhibitor that has shown activity in relapsed or refractory PTCL as a single agent. Its mechanism involves inducing acetylation of histones and other proteins, leading to antitumor effects via increased expression of pro-apoptotic proteins, tumor suppressors, and inhibition of cell growth. CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) is a standard first-line chemotherapy for PTCL, but with limited efficacy on its own. In the Ro-CHOP regimen, romidepsin is administered intravenously (12 mg/m² over 4 hours) on days 1 and 8 of each 3-week cycle for six cycles, alongside the standard CHOP. The combination was evaluated in a phase Ib/II study followed by a randomized phase III trial (Ro-CHOP trial) involving 421 patients with previously untreated PTCL. The primary analysis of the phase III study indicated that adding romidepsin to CHOP did not significantly improve progression-free survival (PFS), response rates, or overall survival compared to CHOP alone. Median PFS was 12.0 months for Ro-CHOP vs. 10.2 months for CHOP (HR 0.81, p=0.096). In the final analysis (median follow-up 6 years), median PFS was 12.0 months vs. 10.2 months (HR 0.79, p=0.054), and median overall survival was 62.2 months vs. 43.8 months (HR 0.88, p=0.324). The addition of romidepsin increased the frequency of grade ≥3 adverse events. Common grade 3/4 events (≥30% incidence in Ro-CHOP) included thrombocytopenia (50% vs. 10% with CHOP), neutropenia (49% vs. 33%), anemia (47% vs. 17%), and leukopenia (32% vs. 20%). Higher toxicity frequently necessitated dose reductions or interruptions, potentially impacting efficacy. An exploratory subgroup analysis in centrally reviewed follicular helper T-cell lymphoma patients suggested a significantly longer median PFS with Ro-CHOP (19.5 months vs. 10.2 months). However, based on the overall results, Romidepsin + CHOP does not represent a significant improvement over standard CHOP for previously untreated PTCL and is not considered a new standard of care.

Brand names

Istodax

Other names

Ro-CHOP