Panobinostat Produces Objective Responses in Patients Refractory to Autologous Transplant

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Panobinostat produced objective responses in 27% and tumor reductions in 74% of 129 patients enrolled in “the largest, prospective, multicenter, international trial conducted in heavily pretreated patients” with Hodgkin lymphoma who relapsed or were refractory to autologous stem cell transplantation, according to results published in the Journal of Clinical Oncology. Among 35 patients achieving objective responses in the phase II trial, 30 had partial responses and 4 had complete responses. The median duration of response was 6.9 months. “An additional 71 patients demonstrated a best response of stable disease, for a disease control rate (complete and partial responses plus stable disease) of 82%,” the researchers reported. The estimated overall survival rate was 78%.

Panobinostat, a pan-deacetylase inhibitor, was administered three times per week orally at a dose of 40 mg to patients who had already received two to seven courses of chemotherapy. The patients were aged 18 years or older from 45 sites across 13 countries. “The population also had many poor prognostic features: 74 patients (57%) had primary refractory disease (did not respond to first-line therapy or relapsed within 3 months) and 85 (66%) relapsed less than 12 months after their first [stem cell transplant],” the authors noted. 

Notable Myelotoxicity

Patients who responded to panobinostat were as heavily pretreated as the overall patient population, and 41% of responders to panobinostat had not responded to their most recent prior therapy. The most common drug-related grade 3 to 4 adverse events “were hematologic and included thrombocytopenia (79%), anemia (21%), and neutropenia (21%),” the authors reported.

“This order of myelotoxicity would certainly limit the ability to combine panobinostat with other myelotoxic drugs,” according to an accompanying editorial. “The relatively low response rate and its toxicity will diminish the enthusiasm for this drug.”

The study’s authors reported that “thrombocytopenia was manageable, commonly through dose or schedule adjustment or study drug interruption, with only seven patients (5%) discontinuing because of thrombocytopenia.” They concluded that not only did panobinostat demonstrate promising single-agent activity, but “because panobinostat modulates several cellular mechanisms that regulate lymphoma cell survival, angiogenesis, and immunity, it has the potential of enhancing the activity of other agents when used in combination.” ■

Younes A, et al: J Clin Oncol April 30, 2012 (early release online).

Canellos GP: J Clin Oncol April 30, 2012 (early release online).




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