I will be reporting on a wide variety of cancer advances as I search through my American Society of Clinical Oncology (ASCO) notes over the next few weeks. So much material to cover–so little time! Here is some promising news about lymphoma treatment advances from ASCO, distributed by M.D. Anderson:
New Lymphoma Drugs Show Promise
By Laura Sussman and Anas Younes, M.D. on June 8, 2010
Two new targeted agents, panobinostat and PCI32765, were presented at ASCO and demonstrated promising clinical activity for the treatment of non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL).
In one study, A. Surrreda presented results from an ongoing large Phase II study of the oral pan histone deacetylase inhibitor (HDACi) in patients with relapsed HL. Remarkably, despite the relative rarity of the patient population, this international trial has completed enrollment with 129 patients at 45 sites in 13 countries.
Oral panobinostat was administered at a dose of 40 mg three times per week, every week, in 21-day cycles. Dose delays and reductions were allowed for management of toxicity. Patients had a median age of 32 years, with a median prior treatment regimens of four. Importantly, 37% had no response on last therapy and 80% had a prior autologous stem cell transplant.
Based on objective response assessment, 17 patients achieved major responses and 71% of the patients had tumor reductions. Common grade 1 and 2 toxicity included nausea, vomiting, and diarrhea. The most common grade 3 and 4 toxicity were thrombocytopenia and anemia. Thus, this study confirms the clinical activity of HDACi in HL.
However, this study is the largest single agent Phase II study to be conducted in patients with relapsed HL, after receiving ASCT, which represents a population of unmet medical need. The final analysis of this study is expected to be available by the end of this year.
While the single agent activity looks very promising, panobinostat-based combination clinical trials are currently enrolling patients with relapsed HL. One interesting study is a combination of everolimus plus panobinostat, which is currently enrolling patients at MD Anderson.
In a second study, N. Fowler presented very exciting data from an ongoing Phase I study using the oral Bruton’s tyrosine Kinase (Btk) inhibitor PCI32765 in patients with relapsed B cell lymphoma. Btk is an important component of B-cell receptor signaling pathway, downstream of Syk.
The first study to target this activated pathway was recently published using the oral Syk inhibitor fostamatinib, which demonstrated promising clinical activity in a variety of B-cell lymphoma, especially chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). Based on promising preclinical data in B-cell NHL, a study was conducted to test the safety, pharmacokinetics, pharmaco-dynamics, and efficacy of PCI-32765, a potent, selective oral inhibitor of Btk.
At the time of the report, 47 patients were enrolled using a dose escalation Phase I design, with a starting dose of 1.25 mg/kg/day. The study included patients with a variety of histologies: 16 follicular, 15 CLL/SLL, seven DLBCL, four mantle, four marginal and one waldenstrom macroglobulinemia. Patients had a median of three prior regimens.
Therapy was well tolerated. Clinical responses were observed in 23% of the patients with FL, 69% with CLL/SLL, 75% of patients with mantle cell lymphoma and in 1/7 patients with DLBCL. Because the MTS has not been reached, dose escalation continues. Thus, PCI-32765 has a favorable safety profile with a promising antitumor activity. This activity will be confirmed in future Phase II studies.
Feel good and keep smiling! Pat