Panobinostat May Be Active in Select Patients With Refractory DLBCL

Among patients with relapsed and refractory diffuse large B-cell lymphoma (DLBCL), 28% of patients achieved a response with panobinostat, a study published inBlood has shown.¹

Panobinostat, a histone deacetylase (HDAC) inhibitor, was approved in 2015 by the U.S. Food and Drug Administration, in combination with bortezomib and dexamethasone, for the treatment of patients with multiple myeloma who have received at least 2 prior regimens.

Because the majority of DLBCL tumors harbor mutations in histone modifying enzymes (HME), there is a potential therapeutic role for HDAC inhibitors in DLBCL. Therefore, researchers sought to evaluate the efficacy and toxicity of panobinostat with or without rituximab, whose effect may be augmented by the panobinostat, in patients with DLBCL.

For the phase 2 study, researchers enrolled 40 patients with relapsed or refractory de novo or transformed DLBCL. Participants received panobinostat 30 mg orally 3 times weekly with or without rituximab. Candidate genes and whole exomes were also sequenced in relapse tumor biopsies to detect for biomarkers that correlate with response.

Results showed that 28% (95% CI, 14.6-43.9) of the 40 patients responded to panobinostat, and researchers found that rituximab did not increase response. The median duration of response was 14.5 months (95% CI, 9.4-not reached). At the time of analysis, 15% of patients had not progressed.

The study further demonstrated that the presence of MEF2B mutations were significantly associated with response to panobinostat. In contrast, an early increase in circulating tumor DNA abundance strongly predicted for treatment failure.                 

Reference

1. Assouline SE, Nielsen TH, Yu S, et al. Phase 2 study of panobinostat +/- rituximab in relapsed diffuse large B cell lymphoma and biomarkers predictive of response [published online ahead of print May 10, 2016]. Blood. doi: 10.1182/blood-2016-02-699520.