A phase I/II dose-escalation study investigating all-oral ixazomib-melphalan-prednisone induction followed by single-agent ixazomib maintenance in transplant-ineligible newly diagnosed multiple myeloma
Jesús F. San-Miguel,
Maria-Asunción Echeveste Gutierrez,
Ivan Špicka,
María-Victoria Mateos,
Kevin Song,
Michael D. Craig,
Joan Bladé,
Roman Hájek,
Christine Chen,
Alessandra Di Bacco,
Jose Estevam,
Neeraj Gupta,
Catriona Byrne,
Vickie Lu,
Helgi van de Velde,
Sagar Lonial
Affiliations
Jesús F. San-Miguel
Clinica Universidad de Navarra, Centro Investigación Medica Aplicada (CIMA), El Instituto de Investigación Sanitaria de Navarra (IDISNA), Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Pamplona, Spain
Maria-Asunción Echeveste Gutierrez
Hospital Universitario Donostia, San Sebastián, Spain
Ivan Špicka
1stMedical Department - Clinical Department of Haematology, First Faculty of Medicine and General Teaching Hospital, Charles University, Prague, Czech Republic
María-Victoria Mateos
Hospital Universitario de Salamanca, Instituto Biosanitario de Salamanca (IBSAL), Spain
Kevin Song
Division of Hematology, University of British Columbia, Vancouver, BC, Canada
Michael D. Craig
Department of Medicine, West Virginia University, Morgantown, WV, USA
Joan Bladé
Department of Hematology, Hospital Clínic de Barcelona, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Spain
Roman Hájek
Department of Haematooncology, University Hospital Ostrava, Faculty of Medicine, Ostrava University, Czech Republic
Christine Chen
Cancer Clinical Research Unit, Princess Margaret Cancer Center, Toronto, ON, Canada
Alessandra Di Bacco
Millennium Pharmaceuticals, Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, Atlanta, GA, USA
Jose Estevam
Millennium Pharmaceuticals, Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, Atlanta, GA, USA
Neeraj Gupta
Millennium Pharmaceuticals, Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, Atlanta, GA, USA
Catriona Byrne
Millennium Pharmaceuticals, Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, Atlanta, GA, USA
Vickie Lu
Millennium Pharmaceuticals, Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, Atlanta, GA, USA
Helgi van de Velde
Millennium Pharmaceuticals, Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, Atlanta, GA, USA
Sagar Lonial
Winship Cancer Institute of Emory University, Atlanta, GA, USA
This phase I/II dose-escalation study investigated the all-oral ixazomib-melphalan-prednisone regimen, followed by single-agent ixazomib maintenance, in elderly, transplant-ineligible patients with newly diagnosed multiple myeloma. Primary phase I objectives were to determine the safety and recommended phase II dose of ixazomib-melphalan-prednisone. The primary phase II objective was to determine the complete plus very good partial response rate. In phase I, patients were enrolled to 4 arms investigating weekly or twice-weekly ixazomib (13 28-day cycles or nine 42-day cycles) plus melphalan-prednisone. In phase II, an expansion cohort was enrolled at the recommended phase II ixazomib dose. Of the 61 patients enrolled, 26 received the recommended phase II dose (ixazomib 4.0 mg [days 1, 8, 15] plus melphalan-prednisone 60 mg/m2 [days 1-4], 28-day cycles). Of the 61 enrolled patients, 36 (13 of 26 in the recommended phase II dose cohort) received single-agent ixazomib maintenance (days 1, 8, 15; 28-day cycles). In phase I, 10/38 patients reported dose-limiting toxicities in cycle 1, including grade 3 and/or 4 neutropenia (n=6) and thrombocytopenia (n=4). Complete plus very good partial response rate was 48% (48% at recommended phase II dose), including 28% (22%) complete response or better; responses deepened during maintenance in 34% (33%) of evaluable patients. After median follow up of 43.6 months, median progression-free survival was 22.1 months. Adverse events were mainly hematologic events, gastrointestinal events, and peripheral neuropathy. This study demonstrates the feasibility, tolerability, and activity of ixazomib-melphalan-prednisone induction and single-agent ixazomib maintenance in transplant-ineligible newly diagnosed multiple myeloma patients. clinicaltrials.gov identifier 01335685.
