PMID- 30471652 OWN - NLM STAT- MEDLINE DCOM- 20200504 LR - 20200505 IS - 1879-0852 (Electronic) IS - 0959-8049 (Linking) VI - 106 DP - 2019 Jan TI - All-oral ixazomib, cyclophosphamide, and dexamethasone for transplant-ineligible patients with newly diagnosed multiple myeloma. PG - 89-98 LID - S0959-8049(18)31381-9 [pii] LID - 10.1016/j.ejca.2018.09.011 [doi] AB - BACKGROUND: Novel efficacious treatments with long-term tolerability are needed for transplant-ineligible, newly diagnosed multiple myeloma (NDMM) patients. This phase 2 study evaluated the safety and efficacy of all-oral ixazomib-cyclophosphamide-dexamethasone (ICd) followed by single-agent ixazomib maintenance. PATIENTS AND METHODS: Patients were randomised (1:1) to receive 4.0 mg of ixazomib, 300 (Arm A) or 400 (Arm B) mg/m(2) of cyclophosphamide (days 1, 8, and 15), and 40 mg of dexamethasone (days 1, 8, 15, and 22) as induction (up to 13 x 28-day cycles), followed by single-agent ixazomib maintenance (28-day cycles) until progressive disease, death, or unacceptable toxicity. Primary end-point was complete response (CR) + very good partial response (VGPR) rate for ICd induction. RESULTS: Seventy patients were enrolled (n = 36 Arm A; n = 34 Arm B); median age was 73 years (range, 61-87). At data cut-off, 66% of patients had completed 13 induction cycles followed by ixazomib maintenance. Median overall treatment duration was 19 cycles (range, 1-29); 21% of patients discontinued treatment during induction and 3% during maintenance due to adverse events (AEs). During induction, among 67 response-evaluable patients, CR+VGPR rate was 25%, and overall response rate (ORR) was 73%. Including the maintenance phase, CR+VGPR rate was 33%, and ORR was 76%. Median progression-free survival was 23.5 months (median follow-up: 26.1 months). The most common all-grade AE was neutropenia (31%). Grade >/=3 AEs were reported by 73% of patients. Five on-study deaths occurred (not treatment-related). CONCLUSIONS: ICd treatment followed by ixazomib maintenance is tolerable and active in elderly, transplant-ineligible NDMM patients. TRIAL REGISTRATION NUMBER: NCT02046070. CI - Copyright (c) 2018. Published by Elsevier Ltd. FAU - Dimopoulos, Meletios A AU - Dimopoulos MA AD - Department of Clinical Therapeutics, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece. Electronic address: mdimop@med.uoa.gr. FAU - Grosicki, Sebastian AU - Grosicki S AD - Department of Cancer Prevention, Silesian Medical University, Katowice, Poland. Electronic address: sgrosicki@wp.pl. FAU - Jedrzejczak, Wieslaw W AU - Jedrzejczak WW AD - Department of Haematology and Oncology, Medical University of Warsaw, Warsaw, Poland. Electronic address: wieslaw.jedrzejczak@wum.edu.pl. FAU - Nahi, Hareth AU - Nahi H AD - Center for Hematology and Regenerative Medicine, Department of Medicine, Karolinska University Hospital, Stockholm, Sweden. Electronic address: hareth.nahi@sll.se. FAU - Gruber, Astrid AU - Gruber A AD - Center for Hematology and Regenerative Medicine, Department of Medicine, Karolinska University Hospital, Stockholm, Sweden. Electronic address: astridgruber7@gmail.com. FAU - Hansson, Markus AU - Hansson M AD - Hematology Clinic, Skane University Hospital, Lund, Sweden; Wallenberg Center for Molecular Medicine, Lund University, Lund, Sweden. Electronic address: markus.hansson@med.lu.se. FAU - Gupta, Neeraj AU - Gupta N AD - Millennium Pharmaceuticals Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, Cambridge, MA, USA. Electronic address: neeraj.gupta@takeda.com. FAU - Byrne, Catriona AU - Byrne C AD - Millennium Pharmaceuticals Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, Cambridge, MA, USA. Electronic address: Catriona.Byrne@takeda.com. FAU - Labotka, Richard AU - Labotka R AD - Millennium Pharmaceuticals Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, Cambridge, MA, USA. Electronic address: Richard.labotka@takeda.com. FAU - Teng, Zhaoyang AU - Teng Z AD - Millennium Pharmaceuticals Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, Cambridge, MA, USA. Electronic address: zhaoyang.teng2@takeda.com. FAU - Yang, Huyuan AU - Yang H AD - Millennium Pharmaceuticals Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, Cambridge, MA, USA. Electronic address: Huyuan.Yang@takeda.com. FAU - Grzasko, Norbert AU - Grzasko N AD - Department of Haematology, St. John's Cancer Centre, Lublin, Poland; Department of Experimental Haemato-oncology, Medical University of Lublin, Lublin, Poland(1). Electronic address: norbertgrzasko@gmail.com. FAU - Kumar, Shaji AU - Kumar S AD - Division of Hematology, Mayo Clinic, Rochester, MN, USA. Electronic address: kumar.shaji@mayo.edu. LA - eng SI - ClinicalTrials.gov/NCT02046070 PT - Clinical Trial, Phase II PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20181122 PL - England TA - Eur J Cancer JT - European journal of cancer (Oxford, England : 1990) JID - 9005373 RN - 0 (Boron Compounds) RN - 71050168A2 (ixazomib) RN - 7S5I7G3JQL (Dexamethasone) RN - 8N3DW7272P (Cyclophosphamide) RN - TE7660XO1C (Glycine) SB - IM MH - Administration, Oral MH - Aged MH - Aged, 80 and over MH - Antineoplastic Combined Chemotherapy Protocols/*administration & dosage/adverse effects MH - Australia MH - Boron Compounds/*administration & dosage/adverse effects MH - Contraindications, Procedure MH - Cyclophosphamide/*administration & dosage/adverse effects MH - Dexamethasone/*administration & dosage/adverse effects MH - Disease Progression MH - Eligibility Determination MH - Europe MH - Female MH - Glycine/administration & dosage/adverse effects/*analogs & derivatives MH - Hematopoietic Stem Cell Transplantation/adverse effects MH - Humans MH - Male MH - Middle Aged MH - Multiple Myeloma/diagnosis/*drug therapy MH - Progression-Free Survival MH - Time Factors MH - United States OTO - NOTNLM OT - Elderly OT - Multiple myeloma OT - Newly diagnosed OT - Oral therapy OT - Transplant-ineligible EDAT- 2018/11/25 06:00 MHDA- 2020/05/06 06:00 CRDT- 2018/11/25 06:00 PHST- 2018/06/27 00:00 [received] PHST- 2018/09/07 00:00 [revised] PHST- 2018/09/15 00:00 [accepted] PHST- 2018/11/25 06:00 [pubmed] PHST- 2020/05/06 06:00 [medline] PHST- 2018/11/25 06:00 [entrez] AID - S0959-8049(18)31381-9 [pii] AID - 10.1016/j.ejca.2018.09.011 [doi] PST - ppublish SO - Eur J Cancer. 2019 Jan;106:89-98. doi: 10.1016/j.ejca.2018.09.011. Epub 2018 Nov 22.