N Murawski1, M Pfreundschuh2, S Zeynalova3, V Poeschel1, M Hänel4, G Held1, N Schmitz5, A Viardot6, C Schmidt7, M Hallek8, M Witzens-Harig9, L Trümper10, T Rixecker1, C Zwick1. 1. Klinik für Innere Medizin I, Universitätsklinikum des Saarlandes, Homburg. 2. Klinik für Innere Medizin I, Universitätsklinikum des Saarlandes, Homburg michael.pfreundschuh@uks.eu. 3. IMISE, University Leipzig, Leipzig. 4. Internal Medicine III, Klinikum Chemnitz, Chemnitz. 5. Department of Haematology, Oncology and Stem Cell Transplantation, Asklepios Klinik St Georg, Hamburg. 6. Innere Medizin, Universitätsklinikum Ulm, Ulm. 7. Klinikum Großhadern, Munich. 8. Universitätsklinik Köln, Cologne. 9. Universitätsklinik Heidelberg, Heidelberg. 10. Universitätsklinikum Göttingen, Göttingen, Germany.
Abstract
BACKGROUND: To improve outcome of elderly patients with diffuse large B-cell lymphoma, dose-dense rituximab was evaluated in the prospective DENSE-R-CHOP-14 trial. PATIENTS AND METHODS: Rituximab (375 mg/m(2)) was given on days 0, 1, 4, 8, 15, 22, 29, 43, 57, 71, 85, and 99 together with six CHOP-14 cycles. Results were to be compared with patients who had received the same chemotherapy in combination with eight 2-week applications of rituximab in RICOVER-60. RESULTS: One hundred twenty-four patients are assessable. Dose-dense rituximab resulted in considerably higher serum levels during the first 50 days of treatment, but rituximab exposure time was not prolonged. Grade 3 and 4 infections were exceptionally high in the first 20 patients without anti-infective prophylaxis, but decreased after introduction of prophylaxis with aciclovir and cotrimoxazole in the remaining 104 patients (from 13% to 6% per cycle and from 35% to 18% per patient; P = 0.007 and P = 0.125, respectively). Patients with international prognostic index = 3-5 had higher complete response/complete response unconfirmed rates (82% versus 68%; P = 0.033) than in the respective RICOVER-60 population, but this did not translate into better long-term outcome, even though male hazard was decreased (event-free survival: from 1.5 to 1.1; progression-free survival: from 1.7 to 1.1; overall survival: from 1.4 to 1.0). CONCLUSIONS: Dose-dense rituximab achieved higher rituximab serum levels, but was not more effective than eight 2-week applications in the historical control population, even though minor improvements in poor-prognosis and male patients cannot be excluded. The increased, though manageable toxicity, precludes its use in routine practice. Our results strongly support anti-infective prophylaxis with aciclovir and cotrimoxazole for all patients receiving R-CHOP.
BACKGROUND: To improve outcome of elderly patients with diffuse large B-cell lymphoma, dose-dense rituximab was evaluated in the prospective DENSE-R-CHOP-14 trial. PATIENTS AND METHODS: Rituximab (375 mg/m(2)) was given on days 0, 1, 4, 8, 15, 22, 29, 43, 57, 71, 85, and 99 together with six CHOP-14 cycles. Results were to be compared with patients who had received the same chemotherapy in combination with eight 2-week applications of rituximab in RICOVER-60. RESULTS: One hundred twenty-four patients are assessable. Dose-dense rituximab resulted in considerably higher serum levels during the first 50 days of treatment, but rituximab exposure time was not prolonged. Grade 3 and 4 infections were exceptionally high in the first 20 patients without anti-infective prophylaxis, but decreased after introduction of prophylaxis with aciclovir and cotrimoxazole in the remaining 104 patients (from 13% to 6% per cycle and from 35% to 18% per patient; P = 0.007 and P = 0.125, respectively). Patients with international prognostic index = 3-5 had higher complete response/complete response unconfirmed rates (82% versus 68%; P = 0.033) than in the respective RICOVER-60 population, but this did not translate into better long-term outcome, even though male hazard was decreased (event-free survival: from 1.5 to 1.1; progression-free survival: from 1.7 to 1.1; overall survival: from 1.4 to 1.0). CONCLUSIONS: Dose-dense rituximab achieved higher rituximab serum levels, but was not more effective than eight 2-week applications in the historical control population, even though minor improvements in poor-prognosis and male patients cannot be excluded. The increased, though manageable toxicity, precludes its use in routine practice. Our results strongly support anti-infective prophylaxis with aciclovir and cotrimoxazole for all patients receiving R-CHOP.
Authors: Ulrich Jaeger; Marek Trneny; Helen Melzer; Michael Praxmarer; Weerasak Nawarawong; Dina Ben Yehuda; David Goldstein; Bilijana Mihaljevic; Osman Ilhan; Veronika Ballova; Michael Hedenus; Liang-Tsai Hsiao; Wing-Yan Au; Sonja Burgstaller; Gerhard Weidinger; Felix Keil; Christian Dittrich; Cathrin Skrabs; Anton Klingler; Andreas Chott; Michael A Fridrik; Richard Greil Journal: Haematologica Date: 2015-04-24 Impact factor: 9.941
Authors: Pieternella Lugtenburg; Irit Avivi; Henriette Berenschot; Osman Ilhan; Jean Pierre Marolleau; Arnon Nagler; Antonio Rueda; Monica Tani; Mehmet Turgut; Stuart Osborne; Rodney Smith; Michael Pfreundschuh Journal: Haematologica Date: 2017-09-21 Impact factor: 9.941