Combining Novel Agents to Treat Lymphoma

Orlando—In the past few years, the US Food and Drug Administration has approved several therapies to treat lymphoma, including rituximab, tositumomab, bortezomib, vorinostat, bendamustine, and pralatrexate. Recently, medical professionals have begun researching the use of combining the novel agents to treat numerous disease types. During a satellite symposium at the American Society of Hematology Annual Meeting and Exposition in December, participants discussed clinical trials and the new therapies in treating T-cell lymphoma, B-cell lymphoma, mantle cell lymphoma, and follicular lymphoma. The symposium was titled Novel Combinations for Lymphoma: Maximizing the Impact of Targeted Therapies. Barbara Pro, MD, Fox Chase Cancer Center, Philadelphia, Pennsylvania, spoke about pralatrexate, an antifolate and the first drug approved to treat peripheral T-cell lymphoma. Several studies have examined pralatrexate’s effectiveness in combination with novel agents gemcitabine, bortezomib, and histone deacetylase inhibitors. According to Dr. Pro, the new agents could overcome the current limitations associated with therapies intended to treat T-cell lymphoma, and researchers are currently examining integrating conventional and novel therapies. However, Dr. Pro said individualized therapy could be more effective. Next, Kieron Dunleavy, MD, National Cancer Institute, Bethesda, Maryland, discussed trials involving standard and novel therapies in treating various types of diffuse large B-cell lymphoma (DLBCL). Dr. Dunleavy said researchers have examined therapies targeting germinal-center B-cell–like lymphoma, B-cell lymphoma 6, activated DLBCL, and primary mediastinal B-cell lymphoma (PMBL). PMBL, a disease often found in young females, is associated with a good prognosis. However, Dr. Dunleavy said the standard treatment for PMBL involves consolidation radiation, which could lead to an increased risk of secondary tumors and ischemic heart disease. Because of the risks, Dr. Dunleavy said researchers must develop therapies other than radiation. Some of the studies that Dr. Dunleavy discussed included an analysis of chemotherapy and bortezomib to treat DLBCL initially and lenalidomide to treat relapsed and refractory DLBCL. He concluded that although DLBCL is molecularly heterogeneous, it is still treated as a single disease. He also mentioned that researchers must determine how to improve outcomes, particularly in nongerminal-center B-cell–like lymphoma tumors. Christian Geisler, MD, Rigshospitalet, Copenhagen, Denmark, then discussed treatment options for mantle cell lymphoma. Standard chemoimmunotherapy includes induction and autologous stem cell transplantation, while targeted therapies include bortezomib, lenalidomide, and mammalian target of rapamycin inhibitors. Studies have shown that patients with mantle cell lymphoma improve when undergoing the standard treatment options, according to Dr. Geisler, who added that there was still room for improvement. He was also encouraged with several ongoing trials involving targeted therapies, including bendamustine, temsirolimus, rituximab, and lenalidomide. Anton Hagen, MD, department of hematology at the University of Amsterdam, the Netherlands, then presented findings from studies involving the treatment of follicular non-Hodgkin’s lymphoma (NHL). He said rituximab has been successful as a first- and second-line treatment in patients with follicular NHL as measured by progression-free survival, overall response rate, and overall survival. However, he warned that not all patients respond well to rituximab or the combination of chemotherapy plus rituximab, with some patients showing progressive disease and/or experiencing a relapse. Dr. Hagen mentioned anti-CD20 monoclonal antibodies, including ofatumumab and ocrelizumab, both of which have better binding compared with rituximab. He also mentioned afutuzumab, another anti-CD20 monoclonal antibody used to treat relapsed or refractory NHL. According to Dr. Hagen, the recommended firstline therapy in treating follicular lymphoma includes rituximab and chemotherapy followed by rituximab maintenance for a maximum of 2 years, while second-line therapy involves rituximab in combination with non–cross-resistant chemotherapy followed by rituximab maintenance for a maximum of 2 years. If patients relapse or have refractory follicular lymphoma, the options include allogeneic stem cell transplantation, radioimmunotherapy, or new monoclonal antibodies. Dr. Hagen said further phase 2 or 3 trials should explore the effectiveness of novel antibodies alone or in combination with chemotherapy. Chris Flowers, MD, assistant professor in the department of hematology and medical oncology at Emory University, Atlanta, Georgia, concluded the presentation by discussing combining targeted therapies to treat lymphoma. He mentioned several investigational therapies for DLBCL, among them bevacizumab, epratuzumab, everolimus, lenalidomide, radioimmunotherapy, MLN4924, tamatinib, bortezomib, and enzastaurin. Dr. Flowers spoke about a few trials involving the agents. For instance, one study showed combining epratuzumab and rituximab in patients with DLBCL led to a response rate of approximately 50%. In addition, he mentioned that adding bortezomib to chemotherapy treatments in patients with follicular lymphoma can lead to improved complete response and molecular complete response rates as well as prolonged relapse-free survival. He also said that a regimen involving the chemotherapy drugs adriamycin, bleomycin, vinblastine, and dacarbazine has proven effective and superior to alternative treatments in numerous trials. Dr. Flowers said that before deciding what novel combinations to use, medical professionals should choose them based on known and hypothesized mechanisms that include biological samples.