Panobinostat monotherapy is active against relapsed or refractory Hodgkin lymphoma.
Major finding: Panobinostat monotherapy is active against relapsed or refractory Hodgkin lymphoma.
Approach: A phase II study evaluated panobinostat safety and efficacy in patients with Hodgkin lymphoma.
Impact: Histone deacetylase inhibitors may be used to treat advanced Hodgkin lymphoma.
There are few treatment options for patients with Hodgkin lymphoma who fail autologous stem-cell transplantation (ASCT). The antibody–drug conjugate brentuximab vedotin was previously approved for treatment of relapsed or ASCT-refractory Hodgkin lymphoma based on a phase II trial. In a search for additional agents that have anti-tumor activity in these patients, Younes and colleagues recently investigated the safety and efficacy of the pan-deacetylase inhibitor panobinostat in 129 heavily pretreated patients with relapsed or refractory Hodgkin lymphoma after ASCT. Panobinostat, which unlike brentuximab vedotin is administered orally, has shown promising activity in early clinical studies against multiple hematologic malignancies, including Hodgkin lymphoma. In the current large, open-label phase II study, the authors observed tumor reductions in 74% of patients and an objective response in 27%. The median progression-free survival was 6.1 months, with an estimated 1-year overall survival rate of 78%. The authors also examined whether expression levels of the cytokine thymus and activation-regulated chemokine (TARC), which is expressed by the pathogenic Hodgkin/Reed-Sternberg cells, may serve as a biomarker of patient response to panobinostat. Interestingly, patients who showed a higher reduction of TARC with treatment had an increased progression-free survival and showed greater disease control than those with low TARC reduction. These findings suggest that TARC levels may represent a biomarker of the clinical activity of panobinostat. Additional studies will elucidate further the potential role of panobinostat in Hodgkin lymphoma treatment.