Pieter Sonneveld1, Hartmut Goldschmidt, Laura Rosiñol, Joan Bladé, Juan José Lahuerta, Michele Cavo, Paola Tacchetti, Elena Zamagni, Michel Attal, Henk M Lokhorst, Avinash Desai, Andrew Cakana, Kevin Liu, Helgi van de Velde, Dixie-Lee Esseltine, Philippe Moreau. 1. Pieter Sonneveld, Erasmus Medical Center, Rotterdam; Henk M. Lokhorst, Utrecht Medical Center, Utrecht, the Netherlands; Hartmut Goldschmidt, University Hospital of Heidelberg, Heidelberg, Germany; Laura Rosiñol, Joan Bladé, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona; Juan José Lahuerta, Hospital Universitario 12 de Octubre, Madrid, Spain; Michele Cavo, Paola Tacchetti, Elena Zamagni, Istituto di Ematologia Seràgnoli, Università degli Studi di Bologna, Bologna, Italy; Michel Attal, Hopital Purpan, Toulouse; Philippe Moreau, University Hospital, Nantes, France; Avinash Desai, Janssen Global Services; Kevin Liu, Janssen Research and Development, Raritan, NJ; Dixie-Lee Esseltine, Millennium Pharmaceuticals, Cambridge, MA; Andrew Cakana, Janssen Research and Development, High Wycombe, United Kingdom; Helgi van de Velde, Janssen Research and Development, Beerse, Belgium.
Abstract
PURPOSE: To characterize efficacy and safety of bortezomib-based versus nonbortezomib-based induction regimens through an integrated analysis of data from phase III studies in transplantation-eligible patients with previously untreated myeloma. PATIENTS AND METHODS: Patient-level data from the IFM 2005-01 (bortezomib-dexamethasone v vincristine-doxorubicin-dexamethasone [VAD] induction), HOVON-65/GMMG-HD4 (bortezomib-doxorubicin-dexamethasone v VAD), and PETHEMA GEM05MENOS65 (bortezomib-thalidomide-dexamethasone v thalidomide-dexamethasone) studies were pooled in an integrated analysis of efficacy and safety. Study-level data from the GIMEMA MM-BO2005 study (bortezomib-thalidomide-dexamethasone v thalidomide-dexamethasone) supplemented the integrated patient-level analysis. Key efficacy end points were post-transplantation complete plus near-complete response (CR+nCR) rate and progression-free survival (PFS). RESULTS: Patient-level data for 1,572 patients (bortezomib-based induction, n = 787; nonbortezomib-based induction, n = 785) were included. Post-transplantation CR+nCR rate was significantly higher following bortezomib-based versus nonbortezomib-based induction (38% v 24%; odds ratio, 2.05; P < .001); the benefit remained similar (pooled odds ratio, 1.96) when GIMEMA MM-BO2005 data were included. Median PFS was 35.9 months versus 28.6 months with bortezomib-based versus nonbortezomib-based induction, respectively (hazard ratio, 0.75; P < .001); 3-year overall survival (OS) rates were 79.7% and 74.7%, respectively (hazard ratio for OS, 0.81; P = .0402). Median duration of induction treatment was 11 weeks in both treatment groups. Rates of peripheral neuropathy during induction were 34% versus 17% (grade ≥ 3, 6% v 1%). Overall, 3% and 4% of patients died during bortezomib-based and nonbortezomib-based induction, respectively. CONCLUSION: Bortezomib-based induction results in significant improvements in response and PFS/OS compared with nonbortezomib-based induction and is generally well tolerated, with a higher rate of peripheral neuropathy but no apparent increase in risk of death during induction.
PURPOSE: To characterize efficacy and safety of bortezomib-based versus nonbortezomib-based induction regimens through an integrated analysis of data from phase III studies in transplantation-eligible patients with previously untreated myeloma. PATIENTS AND METHODS: Patient-level data from the IFM 2005-01 (bortezomib-dexamethasone v vincristine-doxorubicin-dexamethasone [VAD] induction), HOVON-65/GMMG-HD4 (bortezomib-doxorubicin-dexamethasone v VAD), and PETHEMA GEM05MENOS65 (bortezomib-thalidomide-dexamethasone v thalidomide-dexamethasone) studies were pooled in an integrated analysis of efficacy and safety. Study-level data from the GIMEMA MM-BO2005 study (bortezomib-thalidomide-dexamethasone v thalidomide-dexamethasone) supplemented the integrated patient-level analysis. Key efficacy end points were post-transplantation complete plus near-complete response (CR+nCR) rate and progression-free survival (PFS). RESULTS:Patient-level data for 1,572 patients (bortezomib-based induction, n = 787; nonbortezomib-based induction, n = 785) were included. Post-transplantation CR+nCR rate was significantly higher following bortezomib-based versus nonbortezomib-based induction (38% v 24%; odds ratio, 2.05; P < .001); the benefit remained similar (pooled odds ratio, 1.96) when GIMEMA MM-BO2005 data were included. Median PFS was 35.9 months versus 28.6 months with bortezomib-based versus nonbortezomib-based induction, respectively (hazard ratio, 0.75; P < .001); 3-year overall survival (OS) rates were 79.7% and 74.7%, respectively (hazard ratio for OS, 0.81; P = .0402). Median duration of induction treatment was 11 weeks in both treatment groups. Rates of peripheral neuropathy during induction were 34% versus 17% (grade ≥ 3, 6% v 1%). Overall, 3% and 4% of patients died during bortezomib-based and nonbortezomib-based induction, respectively. CONCLUSION:Bortezomib-based induction results in significant improvements in response and PFS/OS compared with nonbortezomib-based induction and is generally well tolerated, with a higher rate of peripheral neuropathy but no apparent increase in risk of death during induction.
Authors: Pieter Sonneveld; Emilie Asselbergs; Sonja Zweegman; Bronno van der Holt; Marie Jose Kersten; Edo Vellenga; Marinus van Marwijk-Kooy; Annemiek Broyl; Okke de Weerdt; Sarah Lonergan; Antonio Palumbo; Henk Lokhorst Journal: Blood Date: 2014-11-14 Impact factor: 22.113
Authors: Parameswaran Hari; Claudia E Paba-Prada; Peter M Voorhees; John Frye; Yu-Lin Chang; Philippe Moreau; Jeffrey Zonder; Ralph Boccia; Kenneth H Shain Journal: Leuk Res Date: 2019-06-17 Impact factor: 3.156
Authors: Sathish Gopalakrishnan; Anita D'Souza; Emma Scott; Raphael Fraser; Omar Davila; Nina Shah; Robert Peter Gale; Rammurti Kamble; Miguel Angel Diaz; Hillard M Lazarus; Bipin N Savani; Gerhard C Hildebrandt; Melhem Solh; Cesar O Freytes; Cindy Lee; Robert A Kyle; Saad Z Usmani; Siddhartha Ganguly; Amer Assal; Jesus Berdeja; Abraham S Kanate; Binod Dhakal; Kenneth Meehan; Tamila Kindwall-Keller; Ayman Saad; Frederick Locke; Sachiko Seo; Taiga Nishihori; Usama Gergis; Cristina Gasparetto; Tomer Mark; Yago Nieto; Shaji Kumar; Parameswaran Hari Journal: Biol Blood Marrow Transplant Date: 2018-12-21 Impact factor: 5.742
Authors: Heinz Ludwig; Pieter Sonneveld; Faith Davies; Joan Bladé; Mario Boccadoro; Michele Cavo; Gareth Morgan; Javier de la Rubia; Michel Delforge; Meletios Dimopoulos; Hermann Einsele; Thierry Facon; Hartmut Goldschmidt; Philippe Moreau; Hareth Nahi; Torben Plesner; Jesús San-Miguel; Roman Hajek; Pia Sondergeld; Antonio Palumbo Journal: Oncologist Date: 2014-07-25
Authors: H Ludwig; J S Miguel; M A Dimopoulos; A Palumbo; R Garcia Sanz; R Powles; S Lentzsch; W Ming Chen; J Hou; A Jurczyszyn; K Romeril; R Hajek; E Terpos; K Shimizu; D Joshua; V Hungria; A Rodriguez Morales; D Ben-Yehuda; P Sondergeld; E Zamagni; B Durie Journal: Leukemia Date: 2013-10-09 Impact factor: 11.528
Authors: Maximilian Merz; Hans Salwender; Mathias Haenel; Elias K Mai; Uta Bertsch; Christina Kunz; Thomas Hielscher; Igor W Blau; Christof Scheid; Dirk Hose; Anja Seckinger; Anna Jauch; Jens Hillengass; Marc S Raab; Baerbel Schurich; Markus Munder; Ingo G H Schmidt-Wolf; Christian Gerecke; Hans-Walter Lindemann; Matthias Zeis; Katja Weisel; Jan Duerig; Hartmut Goldschmidt Journal: Haematologica Date: 2015-04-03 Impact factor: 9.941
Authors: María-Victoria Mateos; Albert Oriol; Laura Rosiñol; Felipe de Arriba; Noemí Puig; Jesús Martín; Joaquín Martínez-López; María Asunción Echeveste; Josep Sarrá; Enrique Ocio; Gemma Ramírez; Rafael Martínez; Luis Palomera; Angel Payer; Rebeca Iglesias; Javier de la Rubia; Adrian Alegre; Ana Isabel Chinea; Joan Bladé; Juan José Lahuerta; Jesús-F San Miguel Journal: Haematologica Date: 2015-04-24 Impact factor: 9.941