BELIEF

Background

Phase II, single-arm, multicenter pivotal study (BELIEF / CLN-19). 129 patients with relapsed/refractory PTCL after ≥1 prior systemic therapy. Belinostat is a pan-HDAC inhibitor (hydroxamic acid class). This study led to FDA accelerated approval of belinostat in R/R PTCL, adding a second HDAC inhibitor option following romidepsin.

Interventions and follow up

Regimen: Belinostat 1000 mg/m² IV days 1–5 every 21d in R/R PTCL
Primary endpoint: Overall response rate (independent review committee)
Median follow-up: ~14 months

Results

ORR (primary): 25.8% (95% CI 18.6–34.1%)
CR rate: 10.8%
Median DoR: 13.6 months
Median PFS: 1.6 months
Median OS: 7.9 months

Adverse events

Hematologic: Grade ≥3 anemia 10.8%; grade ≥3 neutropenia 10.6%; grade ≥3 thrombocytopenia 7.0%
Gastrointestinal/constitutional: Nausea any grade 42.2%; fatigue 37.2%
Cardiac: QTc prolongation <1%, notably lower hematologic toxicity than pralatrexate and romidepsin

Conclusions

Belinostat achieved a 25.8% ORR with a favorable hematologic toxicity profile, notably lower thrombocytopenia (7%) and neutropenia (11%) than other approved PTCL agents, establishing it as a well-tolerated HDAC inhibitor option in R/R PTCL.

Key Limitations

Single-arm Phase II with no randomized comparator; modest ORR (26%) and low CR (11%) with short median PFS (1.6 months) indicate limited durable disease control for most patients. No head-to-head comparison with romidepsin or pralatrexate.

Clinical Context

Belinostat received FDA accelerated approval (2014) for R/R PTCL after ≥1 prior therapy. ESMO guidelines include HDAC inhibitors among options for R/R PTCL; agent choice is largely driven by toxicity profile, with belinostat favored when cytopenias are limiting.

References