Rituximab plus Lenalidomide in Advanced Untreated Follicular Lymphoma
Franck Morschhauser, Nathan H Fowler, Pierre Feugier, Reda Bouabdallah, Hervé Tilly, M Lia Palomba, Christophe Fruchart, Edward N Libby, Rene-Olivier Casasnovas, Ian W Flinn, Corinne Haioun, Hervé Maisonneuve, Loic Ysebaert, Nancy L Bartlett, Kamal Bouabdallah, Pauline Brice, Vincent Ribrag, Nicolas Daguindau, Steven Le Gouill, Gian M Pica, Alejandro Martin Garcia-Sancho, Armando López-Guillermo, Jean-François Larouche, Kiyoshi Ando, Maria Gomes da Silva, Marc André, Pierre Zachée, Laurie H Sehn, Kensei Tobinai, Guillaume Cartron, David Liu, Jianming Wang, Luc Xerri, Gilles A Salles, RELEVANCE Trial Investigators, Nizar Abdel-Samad, May Abdo-Matkiwsky, Julie Abraham, Pau Abrisqueta, Bruno Anglaret, Jeffrey A Barnes, Omar Benbrahim, Philip J Bierman, Christophe Bonnet, Philippe Brault, Dominique Bron, Burke J Brooks Jr, Peter Byeff, Maria Casanova, Matthew Cheung, Yuvraj Choudhary, Terrance Comeau, Barry Cooper, Stephen Couban, Maria Christina Cox, Michael Crump, Bénédicte Deau Fischer, Eric Deconinck, Dries Deeren, Fatima de la Cruz Vicente, Richard Delarue, Raquel Del Campo, Alain Delmer, Vincent Delwail, Peter Raymond Duggan, D Jean-Claude r Mr Eisenmann, Abderrazak El Yamani, Herbert A Eradat, Michel Fabbro, Charles Farber, David C Fisher, Roger A Fleischman, Emmanuel Fleck, Luc-Matthieu Fornecker, Charles Foussard, Jean Gabarre, Yousuf A Gaffar, David Gallardo, Hassan Ghazal, Aristoteles Giagounidis, Karamjit Gill, Sylvie Glaisner, Hugo Gonzalez, Richard H Greenberg, Hadi Goubran Messiha, Andre Goy, Rémy Gressin, Emmanuel Gyan, Lowell L Hart, Kiyohiko Hatake, Wolfgang Hiddemann, Beata Hodossy, Ian Horkheimer, Robert J Hoyer, Kai Huebel, Takayuki Ishikawa, Koji Izutsu, Henry Jardel, Haresh S Jhangiani, Nathalie Johnson, Bertrand Joly, Eric Jourdan, Khalil Kargar Samani, Koji Kato, Toru Kiguchi, Tsutomu Kobayashi, Frédéric Kohser, Michiaki Koike, Tom Kouroukis C, Nicole Laferriere, Thierry Lamy de la Chapelle, Daniel A Landau, William E Lawler, Bernard Lemieux, Denise A Levitan, Luc Longree, Javier Lopez, Joseph Mace, Marie Maerevoet, Michel Maigre, Zora Marjanovic, Jessica Michel, Christiane Mounier, Ana Muntanola, Marie-Christine Ngirabacu, Emmanuelle Nicolas-Virelizier, Silvana Novelli, Fritz Offner, Luis Palomera, Lalita H Pandit, Amit Panwalkar, Pascal Pierre, Jean-Michel Pignon, Antonello Pinto, Christoph Plöger, Delphine Pranger, Donald P Quick, Evangeline A Reyes, Valérie Robin, Daniela Robu, Maria José Rodriguez Salazar, Peter J Rosen, Jonathan Rosenbluth, Sophie Sadot-Lebouvier, Randeep Sangha, Zdenka Segota, Ilan Shapira, Mikhail Shtivelband, Marc Simon, Martin Soekler, Pierre Soubeyran, John Taper, Howard R Tereblo, Maria José Terol, Angelina S The, Yasunori Ueda, Eric van den Neste, Koenraad van Eygen, Achiel van Hoof, Gaetan Vanstraelen, Emma Verner, Pauline Warburton, Go Yamamoto, Hisayuki Yokoyama, Hacene Zerazhi, Pier Luigi Zinzani, Franck Morschhauser, Nathan H Fowler, Pierre Feugier, Reda Bouabdallah, Hervé Tilly, M Lia Palomba, Christophe Fruchart, Edward N Libby, Rene-Olivier Casasnovas, Ian W Flinn, Corinne Haioun, Hervé Maisonneuve, Loic Ysebaert, Nancy L Bartlett, Kamal Bouabdallah, Pauline Brice, Vincent Ribrag, Nicolas Daguindau, Steven Le Gouill, Gian M Pica, Alejandro Martin Garcia-Sancho, Armando López-Guillermo, Jean-François Larouche, Kiyoshi Ando, Maria Gomes da Silva, Marc André, Pierre Zachée, Laurie H Sehn, Kensei Tobinai, Guillaume Cartron, David Liu, Jianming Wang, Luc Xerri, Gilles A Salles, RELEVANCE Trial Investigators, Nizar Abdel-Samad, May Abdo-Matkiwsky, Julie Abraham, Pau Abrisqueta, Bruno Anglaret, Jeffrey A Barnes, Omar Benbrahim, Philip J Bierman, Christophe Bonnet, Philippe Brault, Dominique Bron, Burke J Brooks Jr, Peter Byeff, Maria Casanova, Matthew Cheung, Yuvraj Choudhary, Terrance Comeau, Barry Cooper, Stephen Couban, Maria Christina Cox, Michael Crump, Bénédicte Deau Fischer, Eric Deconinck, Dries Deeren, Fatima de la Cruz Vicente, Richard Delarue, Raquel Del Campo, Alain Delmer, Vincent Delwail, Peter Raymond Duggan, D Jean-Claude r Mr Eisenmann, Abderrazak El Yamani, Herbert A Eradat, Michel Fabbro, Charles Farber, David C Fisher, Roger A Fleischman, Emmanuel Fleck, Luc-Matthieu Fornecker, Charles Foussard, Jean Gabarre, Yousuf A Gaffar, David Gallardo, Hassan Ghazal, Aristoteles Giagounidis, Karamjit Gill, Sylvie Glaisner, Hugo Gonzalez, Richard H Greenberg, Hadi Goubran Messiha, Andre Goy, Rémy Gressin, Emmanuel Gyan, Lowell L Hart, Kiyohiko Hatake, Wolfgang Hiddemann, Beata Hodossy, Ian Horkheimer, Robert J Hoyer, Kai Huebel, Takayuki Ishikawa, Koji Izutsu, Henry Jardel, Haresh S Jhangiani, Nathalie Johnson, Bertrand Joly, Eric Jourdan, Khalil Kargar Samani, Koji Kato, Toru Kiguchi, Tsutomu Kobayashi, Frédéric Kohser, Michiaki Koike, Tom Kouroukis C, Nicole Laferriere, Thierry Lamy de la Chapelle, Daniel A Landau, William E Lawler, Bernard Lemieux, Denise A Levitan, Luc Longree, Javier Lopez, Joseph Mace, Marie Maerevoet, Michel Maigre, Zora Marjanovic, Jessica Michel, Christiane Mounier, Ana Muntanola, Marie-Christine Ngirabacu, Emmanuelle Nicolas-Virelizier, Silvana Novelli, Fritz Offner, Luis Palomera, Lalita H Pandit, Amit Panwalkar, Pascal Pierre, Jean-Michel Pignon, Antonello Pinto, Christoph Plöger, Delphine Pranger, Donald P Quick, Evangeline A Reyes, Valérie Robin, Daniela Robu, Maria José Rodriguez Salazar, Peter J Rosen, Jonathan Rosenbluth, Sophie Sadot-Lebouvier, Randeep Sangha, Zdenka Segota, Ilan Shapira, Mikhail Shtivelband, Marc Simon, Martin Soekler, Pierre Soubeyran, John Taper, Howard R Tereblo, Maria José Terol, Angelina S The, Yasunori Ueda, Eric van den Neste, Koenraad van Eygen, Achiel van Hoof, Gaetan Vanstraelen, Emma Verner, Pauline Warburton, Go Yamamoto, Hisayuki Yokoyama, Hacene Zerazhi, Pier Luigi Zinzani
Abstract
Background: Rituximab plus chemotherapy has been shown to be effective in patients with advanced-stage, previously untreated follicular lymphoma; nevertheless, most patients will have a relapse. Combination immunotherapy with lenalidomide and rituximab is an immunomodulatory regimen that has shown promising activity in patients with indolent B-cell non-Hodgkin's lymphoma.
Methods: We conducted this multicenter, international, phase 3 superiority trial to evaluate rituximab plus lenalidomide, as compared with rituximab plus chemotherapy, in patients with previously untreated follicular lymphoma. Patients were randomly assigned to receive one of the two regimens, followed by maintenance monotherapy with rituximab. Treatment with rituximab plus lenalidomide consisted of 18 cycles of the two drugs, followed by rituximab maintenance therapy every 8 weeks for 12 cycles (six additional doses). Treatment with rituximab plus chemotherapy consisted of the investigator's choice of one of three rituximab-based regimens, followed by maintenance monotherapy with rituximab every 8 weeks for 12 cycles. The primary end points were complete response (confirmed or unconfirmed) at 120 weeks and progression-free survival.
Results: A total of 1030 patients were randomly assigned to receive rituximab plus lenalidomide (513 patients) or rituximab plus chemotherapy (517 patients). The rate of confirmed or unconfirmed complete response at 120 weeks was similar in the two groups: 48% (95% confidence interval [CI], 44 to 53) in the rituximab-lenalidomide group and 53% (95% CI, 49 to 57) in the rituximab-chemotherapy group (P=0.13). The interim 3-year rate of progression-free survival was 77% (95% CI, 72 to 80) and 78% (95% CI, 74 to 82), respectively. A higher percentage of patients in the rituximab-chemotherapy group had grade 3 or 4 neutropenia (32% vs. 50%) and febrile neutropenia of any grade (2% vs. 7%), and a higher percentage of patients in the rituximab-lenalidomide group had grade 3 or 4 cutaneous reactions (7% vs. 1%).
Conclusions: Among patients with previously untreated follicular lymphoma, efficacy results were similar with rituximab plus lenalidomide and rituximab plus chemotherapy (with both regimens followed by rituximab maintenance therapy). The safety profile differed in the two groups. (Funded by Celgene; RELEVANCE ClinicalTrials.gov numbers, NCT01476787 and NCT01650701 , and EudraCT number, 2011-002792-42 .).
Source: PubMed