PMID- 34181755 OWN - NLM STAT- MEDLINE DCOM- 20220308 LR - 20220308 IS - 1097-0142 (Electronic) IS - 0008-543X (Linking) VI - 127 IP - 18 DP - 2021 Sep 15 TI - Carfilzomib, bendamustine, and dexamethasone in patients with advanced multiple myeloma: The EMN09 phase 1/2 study of the European Myeloma Network. PG - 3413-3421 LID - 10.1002/cncr.33647 [doi] AB - BACKGROUND: Combined therapy with carfilzomib, bendamustine, and dexamethasone was evaluated in this multicenter phase 1/2 trial conducted within the European Myeloma Network (EMN09 trial). METHODS: Sixty-three patients with relapsed/refractory multiple myeloma who had received >/=2 lines of prior therapy were included. The phase 1 portion of the study determined the maximum tolerated dose of carfilzomib with bendamustine set at 70 mg/m(2) on days 1 and 8. After 8 cycles, responding patients received maintenance therapy with carfilzomib and dexamethasone until progression. RESULTS: On the basis of the phase 1 results, the recommended phase 2 dose for carfilzomib was 27 mg/m(2) twice weekly in weeks 1, 2, and 3. Fifty-two percent of patients achieved a partial response or better, and 32% reached a very good partial response or better. The clinical benefit rate was 93%. After a median follow-up of 21.9 months, the median progression-free survival was 11.6 months, and the median overall survival was 30.4 months. The reported grade >/=3 hematologic adverse events (AEs) were lymphopenia (29%), neutropenia (25%), and thrombocytopenia (22%). The main nonhematologic grade >/=3 AEs were pneumonia, thromboembolic events (10%), cardiac AEs (8%), and hypertension (2%). CONCLUSIONS: In heavily pretreated patients who have relapsed/refractory multiple myeloma, combined carfilzomib, bendamustine, and dexamethasone is an effective treatment option administered in the outpatient setting. Infection prophylaxis and attention to patients with cardiovascular predisposition are required. CI - (c) 2021 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society. FAU - Gay, Francesca AU - Gay F AD - Myeloma Unit, Division of Hematology, University of Torino, Azienda Ospedaliero Universitaria Citta della Salute e della Scienza, Torino, Italy. FAU - Gunther, Andreas AU - Gunther A AD - Division of Stem Cell Transplantation and Immunotherapy, University of Kiel, Kiel, Germany. FAU - Offidani, Massimo AU - Offidani M AD - Hematology Clinic, AOU Ospedali Riuniti di Ancona, Ancona, Italy. FAU - Engelhardt, Monika AU - Engelhardt M AUID- ORCID: 0000-0003-0405-1676 AD - Department for Hematology and Oncology, University of Freiburg, Faculty of Freiburg, Freiburg, Germany. FAU - Salvini, Marco AU - Salvini M AD - Myeloma Unit, Division of Hematology, University of Torino, Azienda Ospedaliero Universitaria Citta della Salute e della Scienza, Torino, Italy. FAU - Montefusco, Vittorio AU - Montefusco V AD - Hematology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy. FAU - Patriarca, Francesca AU - Patriarca F AD - Hematology and Transplant Unit, University of Udine, Udine, Italy. FAU - Aquino, Sara AU - Aquino S AD - Ematologia e Centro Trapianti, IRCCS Ospedale Policlinico San Martino, Genova, Italy. FAU - Ponisch, Wolfram AU - Ponisch W AD - Department of Hematology, University of Leipzig, Leipzig, Germany. FAU - Spada, Stefano AU - Spada S AD - Myeloma Unit, Division of Hematology, University of Torino, Azienda Ospedaliero Universitaria Citta della Salute e della Scienza, Torino, Italy. FAU - Schub, Natalie AU - Schub N AD - Division of Stem Cell Transplantation and Immunotherapy, University of Kiel, Kiel, Germany. FAU - Gentili, Silvia AU - Gentili S AD - UODS Ematologia AV3, Civitanova Marche, Italy. FAU - Wasch, Ralph AU - Wasch R AD - Department for Hematology and Oncology, University of Freiburg, Faculty of Freiburg, Freiburg, Germany. FAU - Corradini, Paolo AU - Corradini P AD - Hematology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy. FAU - Straka, Christian AU - Straka C AD - Department of Hematology and Oncology, Munich Clinic Schwabing, Munich, Germany. FAU - Palumbo, Antonio AU - Palumbo A AD - Myeloma Unit, Division of Hematology, University of Torino, Azienda Ospedaliero Universitaria Citta della Salute e della Scienza, Torino, Italy. FAU - Einsele, Hermann AU - Einsele H AD - Department of Medicine II, University Hospital of Wurzburg, Wurzburg, Germany. FAU - Boccadoro, Mario AU - Boccadoro M AD - Myeloma Unit, Division of Hematology, University of Torino, Azienda Ospedaliero Universitaria Citta della Salute e della Scienza, Torino, Italy. FAU - Sonneveld, Pieter AU - Sonneveld P AD - Department of Hematology, Erasmus University Medical Center Cancer Institute, Rotterdam, The Netherlands. FAU - Gramatzki, Martin AU - Gramatzki M AUID- ORCID: 0000-0002-6862-2266 AD - Division of Stem Cell Transplantation and Immunotherapy, University of Kiel, Kiel, Germany. LA - eng GR - Onyx/Amgen/ GR - Mundipharma Germany/ GR - HOVON Foundation/ GR - FoNeSa ONLUS/ PT - Clinical Trial, Phase I PT - Clinical Trial, Phase II PT - Journal Article PT - Multicenter Study PT - Research Support, Non-U.S. Gov't DEP - 20210628 PL - United States TA - Cancer JT - Cancer JID - 0374236 RN - 0 (Oligopeptides) RN - 72X6E3J5AR (carfilzomib) RN - 7S5I7G3JQL (Dexamethasone) RN - 981Y8SX18M (Bendamustine Hydrochloride) SB - IM MH - Antineoplastic Combined Chemotherapy Protocols/adverse effects MH - Bendamustine Hydrochloride/adverse effects MH - Dexamethasone MH - Humans MH - *Multiple Myeloma MH - Neoplasm Recurrence, Local/drug therapy MH - Oligopeptides OTO - NOTNLM OT - bendamustine OT - carfilzomib OT - multiple myeloma OT - phase 1/2 study EDAT- 2021/06/29 06:00 MHDA- 2022/03/09 06:00 CRDT- 2021/06/28 17:22 PHST- 2021/03/22 00:00 [revised] PHST- 2020/11/05 00:00 [received] PHST- 2021/04/16 00:00 [accepted] PHST- 2021/06/29 06:00 [pubmed] PHST- 2022/03/09 06:00 [medline] PHST- 2021/06/28 17:22 [entrez] AID - 10.1002/cncr.33647 [doi] PST - ppublish SO - Cancer. 2021 Sep 15;127(18):3413-3421. doi: 10.1002/cncr.33647. Epub 2021 Jun 28.