Michael Pfreundschuh1, Viola Poeschel2, Samira Zeynalova2, Mathias Hänel2, Gerhard Held2, Norbert Schmitz2, Andreas Viardot2, Martin H Dreyling2, Michael Hallek2, Carsten Mueller2, Martin H J Wiesen2, Mathias Witzens-Harig2, Lorenz Truemper2, Ulrich Keller2, Tanja Rixecker2, Carsten Zwick2, Niels Murawski2. 1. Michael Pfreundschuh, Viola Poeschel, Gerhard Held, Tanja Rixecker, Carsten Zwick, and Niels Murawski, Universitätsklinikum des Saarlandes, Homburg; Samira Zeynalova, Leipzig University, Leipzig; Mathias Hänel, Klinikum Chemnitz, Chemnitz; Norbert Schmitz, Asklepios Klinik St Georg, Hamburg; Andreas Viardot, Universitätsklinikum Ulm, Ulm; Martin H. Dreyling, Klinikum Großhadern; Ulrich Keller, Klinikum Rechts der Isar, Munich; Michael Hallek, Carsten Mueller, and Martin H.J. Wiesen, Universitätsklinik Köln, Köln; Mathias Witzens-Harig, Universitätsklinik Heidelberg, Heidelberg; and Lorenz Truemper, Universitätsklinikum Göttingen, Göttingen, Germany. michael.pfreundschuh@uks.eu. 2. Michael Pfreundschuh, Viola Poeschel, Gerhard Held, Tanja Rixecker, Carsten Zwick, and Niels Murawski, Universitätsklinikum des Saarlandes, Homburg; Samira Zeynalova, Leipzig University, Leipzig; Mathias Hänel, Klinikum Chemnitz, Chemnitz; Norbert Schmitz, Asklepios Klinik St Georg, Hamburg; Andreas Viardot, Universitätsklinikum Ulm, Ulm; Martin H. Dreyling, Klinikum Großhadern; Ulrich Keller, Klinikum Rechts der Isar, Munich; Michael Hallek, Carsten Mueller, and Martin H.J. Wiesen, Universitätsklinik Köln, Köln; Mathias Witzens-Harig, Universitätsklinik Heidelberg, Heidelberg; and Lorenz Truemper, Universitätsklinikum Göttingen, Göttingen, Germany.
Abstract
PURPOSE: To study pharmacokinetics, toxicity, and efficacy of prolonged rituximab exposure in elderly patients with diffuse large B-cell lymphoma (DLBCL). PATIENTS AND METHODS: In the SMARTE-R-CHOP-14 trial, rituximab 375 mg/m(2) was administered, together with six cycles of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone on a 14-day schedule (6×R-CHOP-14), on days -4, 0, 10, 29, 57, 99, 155, and 239. Pharmacokinetics and outcome were to be compared with those of patients who had received 6×R-CHOP-14 in combination with eight 2-week applications of rituximab in the RICOVER-60 (Rituximab With CHOP Over Age 60 Years) trial. RESULTS: The complete response (CR)/unconfirmed CR rate was 85% in 189 evaluable patients, 90% for 90 good-prognosis patients (International Prognostic Index [IPI], 1 or 2), and 81% for 99 poor-prognosis patients (IPI, 3 to 5); 3-year event-free survival (EFS) was 71%, 75%, and 67%, respectively; and 3-year overall survival (OS) was 84%, 88%, and 80%, respectively, with no differences between men and women. The preplanned historical comparison with 306 RICOVER-60 patients (good prognosis, n = 183; poor prognosis, n = 123) revealed no outcome differences for all and good-prognosis patients; however, the longer exposure time in SMARTE-R-CHOP-14 compared with RICOVER-60 was associated with better 3-year EFS (67% v 54%) and OS (80% v 67%) in poor-prognosis patients. CONCLUSION: Extended rituximab exposure compared with eight 2-week applications in combination with 6×R-CHOP-14 significantly improved outcome of elderly poor-prognosis patients without increasing toxicity. To our knowledge, results obtained with the SMARTE-R-CHOP-14 rituximab schedule are the best reported for elderly patients with DLBCL to date. In the subgroup of poor-prognosis patients treated with extended rituximab exposure, the outcome seemed superior to that of a similar historical cohort of patients treated with 6×R-CHOP-14 plus 2-week rituximab, with similar toxicity. A randomized comparison of the two schedules is warranted.
PURPOSE: To study pharmacokinetics, toxicity, and efficacy of prolonged rituximab exposure in elderly patients with diffuse large B-cell lymphoma (DLBCL). PATIENTS AND METHODS: In the SMARTE-R-CHOP-14 trial, rituximab 375 mg/m(2) was administered, together with six cycles of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone on a 14-day schedule (6×R-CHOP-14), on days -4, 0, 10, 29, 57, 99, 155, and 239. Pharmacokinetics and outcome were to be compared with those of patients who had received 6×R-CHOP-14 in combination with eight 2-week applications of rituximab in the RICOVER-60 (Rituximab With CHOP Over Age 60 Years) trial. RESULTS: The complete response (CR)/unconfirmed CR rate was 85% in 189 evaluable patients, 90% for 90 good-prognosis patients (International Prognostic Index [IPI], 1 or 2), and 81% for 99 poor-prognosis patients (IPI, 3 to 5); 3-year event-free survival (EFS) was 71%, 75%, and 67%, respectively; and 3-year overall survival (OS) was 84%, 88%, and 80%, respectively, with no differences between men and women. The preplanned historical comparison with 306 RICOVER-60 patients (good prognosis, n = 183; poor prognosis, n = 123) revealed no outcome differences for all and good-prognosis patients; however, the longer exposure time in SMARTE-R-CHOP-14 compared with RICOVER-60 was associated with better 3-year EFS (67% v 54%) and OS (80% v 67%) in poor-prognosis patients. CONCLUSION: Extended rituximab exposure compared with eight 2-week applications in combination with 6×R-CHOP-14 significantly improved outcome of elderly poor-prognosis patients without increasing toxicity. To our knowledge, results obtained with the SMARTE-R-CHOP-14 rituximab schedule are the best reported for elderly patients with DLBCL to date. In the subgroup of poor-prognosis patients treated with extended rituximab exposure, the outcome seemed superior to that of a similar historical cohort of patients treated with 6×R-CHOP-14 plus 2-week rituximab, with similar toxicity. A randomized comparison of the two schedules is warranted.
Authors: Annette M Staiger; Michael Altenbuchinger; Marita Ziepert; Christian Kohler; Heike Horn; Michael Huttner; Katrin S Hüttl; Gunther Glehr; Wolfram Klapper; Monika Szczepanowski; Julia Richter; Harald Stein; Alfred C Feller; Peter Möller; Martin-Leo Hansmann; Viola Poeschel; Gerhard Held; Markus Loeffler; Norbert Schmitz; Lorenz Trümper; Tobias Pukrop; Andreas Rosenwald; German Ott; Rainer Spang Journal: Leukemia Date: 2019-09-17 Impact factor: 11.528
Authors: Grzegorz S Nowakowski; Kristie A Blum; Brad S Kahl; Jonathan W Friedberg; Lawrence Baizer; Richard F Little; David G Maloney; Laurie H Sehn; Michael E Williams; Wyndham H Wilson; John P Leonard; Sonali M Smith Journal: J Natl Cancer Inst Date: 2016-12-16 Impact factor: 13.506
Authors: Luis Malpica; Bolanle Mufuka; Jonathan Galeotti; Xianming Tan; Natalie Grover; Stephen M Clark; Anne Beaven; Hyman Muss; Christopher Dittus Journal: Leuk Lymphoma Date: 2020-02-09
Authors: Zheng Zhou; Alfred W Rademaker; Leo I Gordon; Ann S LaCasce; Allison Crosby-Thompson; Ann Vanderplas; Gregory A Abel; Maria A Rodriguez; Auayporn Nademanee; Mark S Kaminski; Myron S Czuczman; Michael M Millenson; Andrew D Zelenetz; Joyce Niland; Jonathan W Friedberg; Jane N Winter Journal: J Natl Compr Canc Netw Date: 2016-10 Impact factor: 11.908
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: Chadi Nabhan; Xiaolei Zhou; Bann-Mo Day; Keith Dawson; Andrew D Zelenetz; Jonathan W Friedberg; James R Cerhan; Brian K Link; Christopher R Flowers Journal: Am J Hematol Date: 2016-05-24 Impact factor: 10.047