Novel Biological Agents
Take Center Stage

By S. Vincent Rajkumar, M.D.

Over the last few years, a number of novel biological agents have been introduced into the treatment of hematologic malignancies. Imatinib mesylate is a remarkable success story for the treatment of chronic myelogenous leukemia. Similarly, thalidomide and bortezomib represent major successes in the treatment of multiple myeloma. This year, trials report on the activity of various novel biological agents in the treatment of hematologic malignancies. During today’s Simultaneous Session titled Lymphoma: New Agents (3:30 p.m. – 5:30 p.m.), presentations focus on a number of these agents. Dr. Madeleine Duvic and colleagues present a phase II trial of oral suberoylanilide hydroxamic acid (SAHA) for cutaneous T-cell lymphoma (CTCL). In their study, SAHA, a novel small molecular weight inhibitor of class I and class II histone deacetylase, was used in the treatment of CTCL in 13 patients. All patients had relapsed or refractory disease. Five patients (38%) achieved a partial remission and 5 more had stable disease. The authors conclude that SAHA has significant activity in patients with CTCL unresponsive to conventional treatment.

Dr. Andre Goy presents results with bortezomib, a novel proteasome inhibitor, in patients with refractory, indolent, or aggressive lymphomas. Bortezomib (formerly PS341) was recently approved by the FDA for the treatment of relapsed and refractory myeloma in patients who have failed two or more prior regimens. Dr. Goy treated 30 patients on the trial. Eight of 15 patients (53%) with mantle cell lymphoma responded, including three complete responses. In the same session, Dr. Constantine Mitsiades from the Dana-Farber Cancer Institute will present data on the activity of bortezomib in Waldenstrom’s macroglobulinemia.

CC-5013, a novel thalidomide analog, has already shown promise in the treatment of refractory myeloma. Results of a phase I/II trial using another analog, CC-4047, are being presented in tomorrow’s Simultaneous Session Therapeutics for Plasma Cell Dyscrasias (8:00 a.m. – 10:00 a.m.). Of 40 patients treated, 38% achieved a partial response, with at least a 50% or greater reduction in monoclonal protein levels.

The Simultaneous Session on Multiple Myeloma: Developmental Therapeutics (7:30 a.m. – 9:00 a.m.) gives a taste of things to come in the future. Dr. Steve Russell presents a novel strategy using the vaccine strain of the measles virus (MV-EDM) as virotherapy against multiple myeloma in preclinical studies. The vaccine strain is nonpathogenic for humans and is used worldwide for measles vaccination. Although all patients with myeloma would have been vaccinated, circulating anti-measles antibody tires are greatly reduced in the disease. To enhance the anti-myeloma effect, the MV-EDM strain can be engineered to express the sodium iodide symporter (NIS) expressed normally by cells in the thyroid gland. When myeloma cells are infected by this modified MV-NIS strain they acquire the ability to uptake radioiodine, thus enabling noninvasive monitoring of the virus spread by serial gamma camera imaging. This ability can also be exploited for therapeutic advantage with the use of radioactive I131, which will be concentrated by the infected myeloma cells leading to cell death. Based on promising preclinical studies, a phase I trial using this strategy is being planned.