Tag: VELCADE

By Peter Martin, MD

The 50th annual meeting of the American Society of Clinical Oncology took place from May 30-June 3 in Chicago. Over 100 abstracts containing exciting new data were presented. Below is a brief summary of a few abstracts that I found interesting.

KPT-330 (selinexor) appears to be safe and active in patients with heavily pretreated non-Hodgkin lymphoma

Selective inhibitors of nuclear export (SINE) are a new class of cancer drugs that function by suppressing export of proteins and RNA from the cell nucleus into the cell cytoplasm. The accumulation of these molecules in the nucleus results in a multitude of changes that ultimately promote the death of cancer cells, while largely sparing normal cells. Selinexor is a first in class, oral SINE that has been under investigation in multiple hematologic malignancies and solid tumors. Dr. Martin Gutierrez of the John Theurer Cancer Center, presented results from a phase I study of selinexor in patients with heavily pretreated non-Hodgkin lymphoma. This study’s primary objective was to identify an appropriate dose of selinexor for future studies, to evaluate possible side effects, and to evaluate the activity of the drug. At the time of the abstract, 32 patients had received KPT-330 at multiple dose levels over a 28-day cycle. Selinexor was generally well tolerated (side-effects included nausea, loss of appetite, and fatigue) and could be administered over prolonged periods. Importantly, selinexor demonstrated signs of activity in aggressive B-cell and T-cell lymphomas that had otherwise responded poorly to prior therapies. This study is ongoing and is open at WCMC and future trials are planned in DLBCL and patients with CLL and Richter’s transformation.

Bortezomib plus rituximab is well tolerated therapeutic regime that approximates prior long term survival rates for indolent non-Hodgkin lymphoma patients with a high tumor burden

Dr. Andrew M. Evens of Tufts Medical Center, presented results from a phase II trial of bortezomib plus rituximab as a first-line therapy for patients with high tumor burden indolent non-Hodgkin lymphoma. A total of 42 patients with histologies that included follicular lymphoma, marginal zone lymphoma, small lymphocytic lymphoma, and Waldenstrom’s Macroglobulinemia were enrolled. Therapy was well tolerated with few significant side effects, and an overall response rate of 70% (including a complete remission rate of 40%) was observed. Forty-four percent of patients continued to benefit at 4 years, a rate comparable to prior series with rituximab plus cytotoxic chemotherapy. These results suggest that proteasome inhibitors, like bortezomib, have clear activity in follicular lymphoma, a fact that has likely been under appreciated in the past. Nonetheless, whether bortezomib offers any clear benefit over standard chemotherapy remains unclear. Novel proteasome inhibitors that appear to be better tolerated than bortezomib are under evaluation, including this study with oral ixazomib at WCMC.

Bortezomib appears to improve outcomes in patients receiving front-line treatment for mantle cell lymphoma

Rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) remains one of the most common therapies for patients with newly diagnosed mantle cell lymphoma (MCL). In 2006, bortezomib was approved by the FDA for treatment of patients with relapsed MCL. We previously demonstrated that bortezomib could be added to R-CHOP with promising effects . Based on these and other data, investigators in Europe initiated a phase III trial to compare R-CHOP to rituximab, cyclophosphamide, doxorubicin, bortezomib, prednisone (VR-CAP) in patients with previously untreated MCL not eligible for more aggressive therapy. Dr. Franco Cavalli from the Oncology Institute of Southern Switzerland presented the results from this study. A total of 487 patients with treatment naïve, stage II-IV MCL were randomized to receive six to eight cycles R-CHOP or VR-CAP. Patients randomized to treatment with bortezomib achieved significantly longer remission duration with no significant change in side effects. This concept is currently under evaluation in North America in the E1411 trial open at WCMC.

ABT-199 monotherapy shows promise in range of relapsed or refractory non-Hodgkin lymphoma subtypes

ABT-199 is a novel, orally bioavailable, small molecule Bcl-2 inhibitor that has shown promise in the treatment of non-Hodgkin lymphoma (NHL) patients. Dr. Matthew Davids of the Dana-Farber Cancer Institute presented results from a phase I study evaluating the safety and pharmacokinetics profile of ABT-199 in patients with relapsed/refractory NHL. ABT-199 displayed anti-tumor activity across a range of NHL subtypes, most notable in MCL and WM, and at higher doses in DLBCL and FL. Dose escalation is continuing in the phase I study, while subsequent phase II studies are already ongoing in selected histologies.