Bendamustine, thalidomide and dexamethasone combinationtherapy for relapsed/refractory myeloma patients: results ofthe MUKone randomized dose selection trial

There is a signific ant unmet need in effective therapy for relapsed myelomapatients once they become refractory to bortezomib and lenalidomide.While data from the front line setting suggest bendamustine is superior tomelphalan , there is no information defining op timal bendamustine dose inmultiply-treated patients. We report a multi-centre randomized two-stagephase 2 trial simultaneously assessing deliverability and activity of twodoses of bendamustine (60 mg/m2vs. 100 mg/m2) days 1 and 8, thalido -mide (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 ontrial, with a median three prior treatment lines. A pre-planned interimdeliverability and activity assessm ent led to closure of the 100 mg/m2armdue to excess cytopenias, and led to amendment of entry criteria for cy-topenias. Non-haematolo gical toxicities including thromboembolism andneurotoxicity were infrequent. In the 60 mg/m2arm, treatment was deliver-able in 611% subjects and the partial response rate was 463% in the studyeligible population, with 75 months progression-free survival. This studydemonstrates bendamustine at 60 mg/m2twice per month with thalido-mide and dexamethasone is deliverable for repeated cycles in heavily pre-treated myeloma patients and has substantial clinical activity.