Panobinostat in combination with rituximab in heavily pretreated diffuse large B‐cell lymphoma: Results of a phase II study

• Published in: Hematological oncology Vol. 36; no. 4; pp. 633 - 637
• Main Authors: Barnes, Jeffrey A., Redd, Robert, Fisher, David C., Hochberg, Ephraim P., Takvorian, Tak, Neuberg, Donna, Jacobsen, Eric, Abramson, Jeremy S.
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.10.2018
• Subjects: Adult; Aged; Aged, 80 and over; Anemia; Anorexia; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; B-cell lymphoma; Diarrhea; diffuse large B cell lymphoma; Disease-Free Survival; Fatigue; Female; Histone deacetylase; histone deacetylase inhibitor; Humans; Hydroxamic Acids - administration & dosage; Hydroxamic Acids - adverse effects; Hypophosphatemia; Immunotherapy; Indoles - administration & dosage; Indoles - adverse effects; Lymphocytes B; Lymphoma; Lymphoma, Large B-Cell, Diffuse - drug therapy; Lymphoma, Large B-Cell, Diffuse - therapy; Lymphopenia; Male; Middle Aged; Monoclonal antibodies; Nausea; non‐Hodgkin lymphoma; panobinostat; Patients; Recurrence; Rituximab; Rituximab - administration & dosage; Rituximab - adverse effects; Stem Cell Transplantation; Targeted cancer therapy; Thrombocytopenia; Toxicity; non-Hodgkin lymphoma; diffuse large B cell lymphoma; panobinostat; histone deacetylase inhibitor; rituximab
• ISSN: 0278-0232; 1099-1069; 1099-1069
• DOI: 10.1002/hon.2515

This is a phase II study of panobinostat, an oral pan‐HDAC inhibitor, combined with rituximab in patients with relapsed diffuse large B cell lymphoma. Panobinostat was administered orally 3 times a week every other week on a 28‐day cycle. Rituximab was administered weekly during the first cycle, then on Day 1 of cycles 2 to 6. Patients without disease progression after 6 cycles continued panobinostat monotherapy for up to 6 additional cycles in the absence of disease progression. Eighteen eligible subjects were enrolled, and 18 were evaluable for response. The overall response rate was 11% (90% CI [2%‐34%]) with 2 subjects having a partial response. The duration of response in these subjects was 51 and 60 days. Five additional subjects had stable disease with 3 subjects having tumor reduction between 27 and 44%, not meeting criteria for partial response. One subject with stable disease remained on therapy a total of 12 cycles. The most common toxicities while on study were thrombocytopenia (14 patients, 78%); fatigue (11, 61%); anemia (10, 56%); diarrhea (8, 44%); and nausea, lymphopenia, anorexia, and hypophosphatemia (5 each, 28% of patients), the majority of which was grade 2 or less. These data indicate that the combination of panobinostat with rituximab is able to induce responses in a limited number of subjects with relapsed diffuse large B cell lymphoma.