Efficacy and safety of ifupinostat in relapsed or refractory diffuse large B-cell lymphoma: a multicenter, single-arm phase 2 study.

In 30 seconds

This multicenter, single-arm phase 2 study evaluated intravenous ifupinostat monotherapy in patients with relapsed or refractory diffuse large B-cell lymphoma after at least two prior systemic therapy lines. Among 115 patients in the efficacy analysis set, blinded independent central review found an objective response rate of 36.5% (42/115, 95% CI 27.7-46.0), including complete responses in 11.3% (13/115). Median progression-free survival was 2.7 months and median overall survival was 9.9 months. Treatment-related adverse events were frequent, with grade 3 or higher events in 86.7% of the safety set.

Key findings

• Objective response rate was 36.5% (42/115, 95% CI 27.7-46.0); complete response rate was 11.3% (13/115).
• Median duration of response was 6.2 months (95% CI 3.5-14.5), median progression-free survival 2.7 months (95% CI 1.6-3.7), and median overall survival 9.9 months (95% CI 7.8-14.8).
• Treatment-related adverse events occurred in 99.2% (127/128); grade 3 or higher events occurred in 86.7% (111/128).
• The most common grade 3 or higher treatment-related events were thrombocytopenia (75.8%, 97/128), neutropenia (33.6%, 43/128), and leukopenia (22.7%, 29/128); no treatment-related deaths occurred.

Why it matters

Relapsed or refractory DLBCL after multiple prior treatment lines remains a setting in which response and tolerability are clinically important. This study provides prospective evidence of antitumour activity for a dual HDAC and PI3Kα inhibitor, alongside substantial treatment-related toxicity. The response and survival outcomes help characterize the potential and risks of this investigational monotherapy in a heavily pretreated population.

What to keep in mind

The study was single-arm, so it cannot establish comparative benefit against other treatments. The efficacy analysis included 115 patients, fewer than the 128 in the safety set.