title: Bendamustine, thalidomide and dexamethasone combination therapy for relapsed/refractory myeloma patients: results of the MUKone randomized dose selection trial.
abstract: There is a significant unmet need in effective therapy for relapsed myeloma patients once they become refractory to bortezomib and lenalidomide. While data from the front line setting suggest bendamustine is superior to melphalan, there is no information defining optimal bendamustine dose in multiply-treated patients. We report a multi-centre randomized two-stage phase 2 trial simultaneously assessing deliverability and activity of two doses of bendamustine (60 mg/m2 vs. 100 mg/m2) days 1 and 8, thalidomide (100 mg) days 1-21 and low dose dexamethasone (20 mg) days 1, 8, 15 and 22 of a 28-d cycle. Ninety-four relapsing patients were treated on trial, with a median three prior treatment lines. A pre-planned interim deliverability and activity assessment led to closure of the 100 mg/m2 arm due to excess cytopenias, and led to amendment of entry criteria for cytopenias. Non-haematological toxicities including thromboembolism and neurotoxicity were infrequent. In the 60 mg/m2 arm, treatment was deliverable in 61.1% subjects and the partial response rate was 46.3% in the study eligible population, with 7.5 months progression-free survival. This study demonstrates bendamustine at 60 mg/m2 twice per month with thalidomide and dexamethasone is deliverable for repeated cycles in heavily pre-treated myeloma patients and has substantial clinical activity.
authors.affiliation: Department of Haematology, King's College Hospital, London, UK.
authors.forename: Steve
authors.initials: S
authors.lastname: Schey
authors.affiliation: Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK.
authors.forename: Sarah R
authors.initials: SR
authors.lastname: Brown
authors.affiliation: Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK.
authors.forename: Avie-Lee
authors.initials: AL
authors.lastname: Tillotson
authors.affiliation: University College London Cancer Institute, London, UK.
authors.forename: Kwee
authors.initials: K
authors.lastname: Yong
authors.affiliation: Centre for Clinical Haematology, Nottingham University Hospitals, Nottingham, UK.
authors.forename: Cathy
authors.initials: C
authors.lastname: Williams
authors.affiliation: Haemato-Oncology Unit, Royal Marsden NHS Foundation Trust, Sutton, UK.
authors.forename: Faith
authors.initials: F
authors.lastname: Davies
authors.affiliation: Haemato-Oncology Unit, Royal Marsden NHS Foundation Trust, Sutton, UK.
authors.forename: Gareth
authors.initials: G
authors.lastname: Morgan
authors.affiliation: Department of Haematology, St Bartholomew's Hospital, London, UK.
authors.forename: Jamie
authors.initials: J
authors.lastname: Cavenagh
authors.affiliation: Department of Haematology, St James's University Hospital, Leeds, UK.
authors.forename: Gordon
authors.initials: G
authors.lastname: Cook
authors.affiliation: Queen Elizabeth Hospital, Birmingham, UK.
authors.forename: Mark
authors.initials: M
authors.lastname: Cook
authors.affiliation: Department of Haematology, King's College Hospital, London, UK.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Orti
authors.affiliation: The Queens University Belfast, Belfast, UK.
authors.forename: Curly
authors.initials: C
authors.lastname: Morris
authors.affiliation: Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK.
authors.forename: Debbie
authors.initials: D
authors.lastname: Sherratt
authors.affiliation: Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK.
authors.forename: Louise
authors.initials: L
authors.lastname: Flanagan
authors.affiliation: Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK.
authors.forename: Walter
authors.initials: W
authors.lastname: Gregory
authors.affiliation: Haematology and Transplant Unit, Christie NHS Foundation Trust, Manchester, UK.
authors.forename: James
authors.initials: J
authors.lastname: Cavet
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D000069461:Bendamustine Hydrochloride; D003907:Dexamethasone / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000401:mortality*; D009588:Nitrogen Mustard Compounds / Q000008:administration & dosage / Q000009:adverse effects; D015996:Survival Rate; D013792:Thalidomide / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D009588:Nitrogen Mustard Compounds; D013792:Thalidomide; D003907:Dexamethasone; D000069461:Bendamustine Hydrochloride
keywords: bendamustine; dosing; myeloma; phase 2; relapsed-refractory