Literature DB >> 31160237

Carfilzomib-Dexamethasone Versus Bortezomib-Dexamethasone in Relapsed or Refractory Multiple Myeloma: Updated Overall Survival, Safety, and Subgroups.

Robert Z Orlowski1, Philippe Moreau2, Ruben Niesvizky3, Heinz Ludwig4, Albert Oriol5, Wee Joo Chng6, Hartmut Goldschmidt7, Zhao Yang8, Amy S Kimball9, Meletios Dimopoulos10.   

Abstract

INTRODUCTION: The phase III RandomizEd, OpeN Label, Phase 3 Study of Carfilzomib Plus DExamethAsone Vs Bortezomib Plus DexamethasOne in Patients With Relapsed Multiple Myeloma (ENDEAVOR) trial showed significantly improved progression-free survival and overall survival (OS) with carfilzomib (56 mg/m2) and dexamethasone (Kd56) versus bortezomib and Kd56 (Vd) in patients with relapsed or refractory multiple myeloma (RRMM). We report updated OS and safety data after 6 months of additional follow-up. PATIENTS AND METHODS: Patients with RRMM (1-3 previous lines of therapy) were randomized 1:1 to Kd56 or Vd. Median OS was estimated using the Kaplan-Meier method; OS was compared between treatment groups using Cox proportional hazards models.
RESULTS: As of July 19, 2017, median follow-up was 44.3 months for Kd56 and 43.7 months for Vd. Median OS was 47.8 months (Kd56) versus 38.8 months (Vd; hazard ratio, 0.76; 95% confidence interval, 0.633-0.915). OS was longer with Kd56 versus Vd within age and cytogenetic subgroups, and according to number of previous lines of therapy, previous bortezomib exposure, previous lenalidomide exposure, and lenalidomide-refractory status. Exposure-adjusted incidences per 100 patient-years of adverse events (AEs) were 1352.07 for Kd56 and 1754.86 for Vd; for Grade ≥3 AEs, these values were 162.31 and 175.90.
CONCLUSION: With median follow-up of approximately 44 months, clinically meaningful improvements in OS were observed with Kd56 versus Vd, including in all subgroups examined. The Kd56 safety profile was consistent with previous analyses.
Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.

Entities:  

Keywords:  Clinical outcomes; Efficacy; Phase III; Proteasome inhibitor

Year:  2019        PMID: 31160237     DOI: 10.1016/j.clml.2019.04.018

Source DB:  PubMed          Journal:  Clin Lymphoma Myeloma Leuk        ISSN: 2152-2669


  13 in total

1.  CD38 deletion of human primary NK cells eliminates daratumumab-induced fratricide and boosts their effector activity.

Authors:  Meisam Naeimi Kararoudi; Yuya Nagai; Ezgi Elmas; Marcelo de Souza Fernandes Pereira; Syed Abbas Ali; Philip Hollingsworth Imus; Darren Wethington; Ivan Marques Borrello; Dean Anthony Lee; Gabriel Ghiaur
Journal:  Blood       Date:  2020-11-19       Impact factor: 22.113

2.  Clinical impacts of frailty, poor performance status, and advanced age in carfilzomib-containing treatment for relapsed/refractory multiple myeloma: post hoc investigation of the KOTOSG multicenter pilot prospective observational study.

Authors:  Yuka Kawaji-Kanayama; Ayako Muramatsu; Nana Sasaki; Kazuho Shimura; Miki Kiyota; Shinichi Fuchida; Reiko Isa; Takahiro Fujino; Yayoi Matsumura-Kimoto; Taku Tsukamoto; Yoshiaki Chinen; Shinsuke Mizutani; Mitsushige Nakao; Hiroto Kaneko; Eri Kawata; Koichi Hirakawa; Ryoichi Takahashi; Chihiro Shimazaki; Hitoji Uchiyama; Nobuhiko Uoshima; Yuji Shimura; Tsutomu Kobayashi; Masafumi Taniwaki; Junya Kuroda
Journal:  Int J Hematol       Date:  2022-01-24       Impact factor: 2.490

Review 3.  Gaps and opportunities in the treatment of relapsed-refractory multiple myeloma: Consensus recommendations of the NCI Multiple Myeloma Steering Committee.

Authors:  Shaji Kumar; Lawrence Baizer; Natalie S Callander; Sergio A Giralt; Jens Hillengass; Boris Freidlin; Antje Hoering; Paul G Richardson; Elena I Schwartz; Anthony Reiman; Suzanne Lentzsch; Philip L McCarthy; Sundar Jagannath; Andrew J Yee; Richard F Little; Noopur S Raje
Journal:  Blood Cancer J       Date:  2022-06-29       Impact factor: 9.812

4.  Real-world effectiveness and safety analysis of carfilzomib-lenalidomide-dexamethasone and carfilzomib-dexamethasone in relapsed/refractory multiple myeloma: a multicenter retrospective analysis.

Authors:  Yoshiyuki Onda; Junya Kanda; Hitomi Kaneko; Yuji Shimura; Shin-Ichi Fuchida; Aya Nakaya; Tomoki Itou; Ryosuke Yamamura; Hirokazu Tanaka; Hirohiko Shibayama; Yutaka Shimazu; Hitoji Uchiyama; Satoshi Yoshihara; Yoko Adachi; Mitsuhiro Matsuda; Hitoshi Hanamoto; Nobuhiko Uoshima; Satoru Kosugi; Kensuke Ohta; Hideo Yagi; Yuzuru Kanakura; Itaru Matsumura; Masayuki Hino; Shosaku Nomura; Chihiro Shimazaki; Akifumi Takaori-Kondo; Junya Kuroda
Journal:  Ther Adv Hematol       Date:  2022-06-24

Review 5.  Patients With Multiple Myeloma or Monoclonal Gammopathy of Undetermined Significance.

Authors:  Vanessa Piechotta; Nicole Skoetz; Monika Engelhardt; Hermann Einsele; Hartmut Goldschmidt; Christof Scheid
Journal:  Dtsch Arztebl Int       Date:  2022-04-08       Impact factor: 8.251

6.  Efficacy and safety profile of deep responders to carfilzomib-based therapy: a subgroup analysis from ASPIRE and ENDEAVOR.

Authors:  Katja Weisel; Maria-Victoria Mateos; Francesca Gay; Michel Delforge; Gordon Cook; Zsolt Szabo; Renaud Desgraz; Lucy DeCosta; Philippe Moreau
Journal:  Leukemia       Date:  2020-10-16       Impact factor: 11.528

Review 7.  The changing landscape of relapsed and/or refractory multiple myeloma (MM): fundamentals and controversies.

Authors:  José-Ángel Hernández-Rivas; Rafael Ríos-Tamayo; Cristina Encinas; Rafael Alonso; Juan-José Lahuerta
Journal:  Biomark Res       Date:  2022-01-09

8.  Elucidating Carfilzomib's Induced Cardiotoxicity in an In Vivo Model of Aging: Prophylactic Potential of Metformin.

Authors:  Panagiotis Efentakis; Garyfalia Psarakou; Aimilia Varela; Eleni Dimitra Papanagnou; Michail Chatzistefanou; Panagiota-Efstathia Nikolaou; Costantinos H Davos; Maria Gavriatopoulou; Ioannis P Trougakos; Meletios Athanasios Dimopoulos; Ioanna Andreadou; Evangelos Terpos
Journal:  Int J Mol Sci       Date:  2021-10-11       Impact factor: 5.923

9.  In response to: Treatment of patients with multiple myeloma progressing on frontline therapy with lenalidomide, Moreau et al., 2019.

Authors:  Zandra Klippel; Amy Kimball; Christina Tekle
Journal:  Blood Cancer J       Date:  2019-11-19       Impact factor: 11.037

10.  Prognostic impact of resistance to bortezomib and/or lenalidomide in carfilzomib-based therapies for relapsed/refractory multiple myeloma: The Kyoto Clinical Hematology Study Group, multicenter, pilot, prospective, observational study in Asian patients.

Authors:  Yuka Kawaji-Kanayama; Tsutomu Kobayashi; Ayako Muramatsu; Hitoji Uchiyama; Nana Sasaki; Nobuhiko Uoshima; Mitsushige Nakao; Ryoichi Takahashi; Kazuho Shimura; Hiroto Kaneko; Miki Kiyota; Katsuya Wada; Yoshiaki Chinen; Koichi Hirakawa; Shin-Ichi Fuchida; Chihiro Shimazaki; Yayoi Matsumura-Kimoto; Shinsuke Mizutani; Taku Tsukamoto; Yuji Shimura; Shigeo Horiike; Masafumi Taniwaki; Junya Kuroda
Journal:  Cancer Rep (Hoboken)       Date:  2021-06-14
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