PMID- 37996265 OWN - NLM STAT- MEDLINE DCOM- 20240202 LR - 20240410 IS - 2152-2669 (Electronic) IS - 2152-2669 (Linking) VI - 24 IP - 2 DP - 2024 Feb TI - Use Via Early Access to Ixazomib (UVEA-IXA) Study: Effectiveness and Safety of Ixazomib-based Therapy in Relapsed/Refractory Multiple Myeloma Outside of the Clinical Trial Setting. PG - e40-e49.e3 LID - S2152-2650(23)02148-1 [pii] LID - 10.1016/j.clml.2023.10.003 [doi] AB - BACKGROUND: In multiple myeloma (MM), improving our understanding of routine clinical practice and the effectiveness of agents outside of clinical trials is important. TOURMALINE-MM1 data resulted in approval of ixazomib for MM patients who have received >/= 1 prior therapy. PATIENTS AND METHODS: UVEA-IXA comprised a retrospective chart review in the early access program, and a prospective 1-year follow-up period. Eligible patients had had a biochemical and/or symptomatic relapse after 1-3 prior lines of therapy; no anti-MM therapy for > 3 cycles at the start of ixazomib therapy; and an Eastern Cooperative Oncology Group performance score of 0-2. Lenalidomide- or proteasome inhibitor (PI)-refractory patients were ineligible. Primary endpoints were response and progression-free survival (PFS). RESULTS: Of 357 enrolled patients, 309 were evaluable; most patients received ixazomib alongside lenalidomide (98%) and dexamethasone (97%); 61% had received 2-3 prior lines of therapy. Median PFS was 15.6 months (95% confidence interval [CI]: 12.0-20.6) in all evaluable patients, and 19.6 (95% CI: 12.1-27.0) and 13.9 (95% CI: 10.1-18.1) months in patients who received 1 and >/= 2 prior lines of therapy, respectively. The overall response rate was 67% in all evaluable patients, and 72% and 63%, respectively, in patients who received 1 and >/= 2 prior lines of therapy. Median overall survival was 35.5 months. The ixazomib safety profile was consistent with previous reports. CONCLUSION: This study supports ixazomib-based therapy as an effective and tolerable treatment in the real-world. Outcomes were favorable in patients with 1 or >/= 2 prior lines of therapy who were not lenalidomide- or PI-refractory. CI - Copyright (c) 2023 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Ludwig, Heinz AU - Ludwig H AD - First Department of Medicine, Wilhelminen Cancer Research Institute, Center for Oncology and Hematology, Clinic Ottakring, Vienna, Austria. Electronic address: heinz.ludwig@extern.gesundheitsverbund.at. FAU - Ramasamy, Karthik AU - Ramasamy K AD - Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom. FAU - Mateos, Maria-Victoria AU - Mateos MV AD - Department of Hematology, University Hospital of Salamanca, IBSAL, CIC, IBMCC (USAL-CSIC), Salamanca, Spain. FAU - Kishore, Bhuvan AU - Kishore B AD - Heart of England/University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom. FAU - Gergely, Varga AU - Gergely V AD - Faculty of Medicine Department of Internal Medicine and Haematology, Semmelweis University, Budapest, Hungary. FAU - Ladicka, Miriam AU - Ladicka M AD - National Cancer Institute, Bratislava, Slovakia. FAU - Ori, Alessandra AU - Ori A AD - MediNeos, Observational Research, Modena, Italy. FAU - Simoni, Lucia AU - Simoni L AD - MediNeos, Observational Research, Modena, Italy. FAU - Bent-Ennakhil, Nawal AU - Bent-Ennakhil N AD - Takeda Pharmaceuticals International AG, Zurich, Switzerland. FAU - Stull, Dawn Marie AU - Stull DM AD - Takeda Pharmaceuticals U.S.A., Inc., Lexington, MA. FAU - Gavini, Francois AU - Gavini F AD - Takeda Pharmaceuticals International AG, Zurich, Switzerland. FAU - Terpos, Evangelos AU - Terpos E AD - Department of Clinical Therapeutics, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece. FAU - Hajek, Roman AU - Hajek R AD - Department of Hematooncology, University Hospital Ostrava, Ostrava, Czech Republic; Department of Haematooncology, Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20231014 PL - United States TA - Clin Lymphoma Myeloma Leuk JT - Clinical lymphoma, myeloma & leukemia JID - 101525386 RN - F0P408N6V4 (Lenalidomide) RN - 71050168A2 (ixazomib) RN - 7S5I7G3JQL (Dexamethasone) RN - 0 (Boron Compounds) RN - TE7660XO1C (Glycine) SB - IM MH - Humans MH - *Multiple Myeloma MH - Lenalidomide/therapeutic use MH - Retrospective Studies MH - Prospective Studies MH - Dexamethasone/therapeutic use MH - Neoplasm Recurrence, Local/drug therapy MH - Antineoplastic Combined Chemotherapy Protocols/adverse effects MH - Uvea MH - *Boron Compounds MH - Glycine/*analogs & derivatives OTO - NOTNLM OT - Cohort study OT - Early access program OT - Europe OT - Overall response rate OT - Progression-free survival COIS- Disclosures HL received research funding from Amgen and Sanofi; received payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing or educational events from Celgene-BMS, Janssen-Cilag, Sanofi, Amgen, Takeda, and AbbVie; participated on a Data Safety Monitoring Board or Advisory Board for Celgene-BMS, Janssen-Cilag, Sanofi, Amgen, Takeda, and AbbVie. KR received grant funding to his institution from Janssen, Amgen, Takeda, GSK, and Celgene-BMS; received honoraria from Janssen, Adaptive Biotech, Amgen, Takeda, AbbVie, Oncopeptides, Celgene-BMS, Pfizer, and GSK; received support for attending meetings and/or travel from BMS, Amgen, and Takeda; participated on Advisory Boards for Janssen, Adaptive Biotech, Amgen, Takeda, AbbVie, Oncopeptides, Celgene-BMS, Pfizer, and GSK. M-VM received payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing or educational events from Janssen, Celgene, Takeda, Amgen, GSK, AbbVie, Pfizer, Regeneron, Roche, Sanofi, Oncopeptides, and Steamline; participated on a Data Safety Monitoring Board or Advisory Board for Janssen, Celgene, Sanofi, Takeda, GSK, Pfizer, Roche, and Steamline. ML received payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing or educational events from Sandoz, Janssen, Takeda, and Amgen; participated on a Data Safety Monitoring Board or Advisory Board for Novartis, Janssen, Takeda, and Amgen. AO and LS are employees of MediNeos, the contract-research organization which was involved by Takeda EUCAN for the design, conduction, and analysis of the study. N-BE is a Takeda employee and hold shares in Takeda. DMS was a Takeda employee and held stock in Takeda when the study was conducted and the manuscript was developed; received support for the present manuscript from Takeda. FG is a Takeda employee and hold shares and stock in Takeda; received support for the present manuscript from Takeda. ET received support for the present manuscript from Takeda; received grants or contracts from Amgen, GSK, Janssen, Sanofi, and Takeda; received payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing or educational events from Amgen, Astra Zeneca, BMS, GSK, Janssen, Menarini, Novartis, Pfizer, Sanofi, and Takeda; received support for attending meetings and/or travel from Amgen, EUSA Pharma, and Takeda; participated on a Data Safety Monitoring Board or Advisory Board for BMS, GSK, Janssen, Sanofi, and Takeda. RH received grants/contracts to his institution from Janssen, Amgen, Celgene, BMS, Novartis, and Takeda; received consulting fees from Janssen, Amgen, Celgene, AbbVie, BMS, Novartis, PharmaMar, and Takeda; received payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing or educational events from Janssen, Amgen, Celgene, BMS, PharmaMar, and Takeda; received support for attending meetings and/or travel from Amgen, Celgene, Takeda, Janssen; participated on a Data Safety Monitoring Board or Advisory Board for BMS, Takeda, Amgen, Oncopeptides, Sanofi, Janssen, GSK. BK and VG have nothing to disclose. Steering committee membership: KR, NB-E, ET. EDAT- 2023/11/24 00:42 MHDA- 2024/02/02 06:43 CRDT- 2023/11/23 21:59 PHST- 2023/06/30 00:00 [received] PHST- 2023/09/26 00:00 [revised] PHST- 2023/10/11 00:00 [accepted] PHST- 2024/02/02 06:43 [medline] PHST- 2023/11/24 00:42 [pubmed] PHST- 2023/11/23 21:59 [entrez] AID - S2152-2650(23)02148-1 [pii] AID - 10.1016/j.clml.2023.10.003 [doi] PST - ppublish SO - Clin Lymphoma Myeloma Leuk. 2024 Feb;24(2):e40-e49.e3. doi: 10.1016/j.clml.2023.10.003. Epub 2023 Oct 14.