title: Upfront lower dose lenalidomide is less toxic and does not compromise efficacy for vulnerable patients with relapsed refractory multiple myeloma: final analysis of the phase II RevLite study.
abstract: The combination of lenalidomide and dexamethasone is an established treatment for patients with multiple myeloma (MM). Increasingly, treatment attenuation is advocated for frail/elderly patients to minimize toxicity even though there have been no prospective studies to demonstrate whether lenalidomide dose attenuation impacts on response and survival outcome. This prospective multicentre phase II study assessed the efficacy and tolerability of lower dose lenalidomide (15 mg) and dexamethasone (20 mg) in 149 eligible patients with relapsed/refractory MM aged over 59 years and/or with renal impairment. The overall response rate was 71% (complete response 15%). Median (range) progression-free survival (PFS) and overall survival (OS) were 8·9 (6·9-11·5) and 30·5 (20·0-36·2) months, respectively. Upon formal statistical comparison of these endpoints to that of a matched cohort of patients from the pivotal phase III MM009/MM010 studies who received standard-dose lenalidomide (25 mg) and high-dose dexamethasone (40 mg) no difference was seen in PFS (P = 0·34) and OS (P = 0·21). Importantly, grade 3-4 toxicities were reduced with low-dose lenalidomide, mainly lower neutropenia (29% vs. 41%), infections (23% vs. 31%) and venous thromboembolism (3% vs. 13%). This study supports a strategy of lenalidomide dose reduction at the outset for at-risk patients, and prospectively confirms that such an approach reduces adverse events while not compromising patient response or survival outcomes.
authors.affiliation: Faculty of Medicine, University of Melbourne, Victoria, Australia.|Department of Haematology, St. Vincent's Hospital Melbourne, Melbourne, Vic., Australia.
authors.forename: Hang
authors.initials: H
authors.lastname: Quach
authors.affiliation: Weill Cornell Medical College, Doha, Qatar.
authors.forename: Liam
authors.initials: L
authors.lastname: Fernyhough
authors.affiliation: Department of Medicine, Royal North Shore Hospital, Saint Leonards, NSW, Australia.
authors.forename: Ross
authors.initials: R
authors.lastname: Henderson
authors.affiliation: Department of Medicine, Tauranga Hospital, Tauranga, New Zealand.
authors.forename: Gillian
authors.initials: G
authors.lastname: Corbett
authors.affiliation: Department of Haematology, Palmerston North Hospital, Palmerston North, New Zealand.
authors.forename: Bart
authors.initials: B
authors.lastname: Baker
authors.affiliation: Department of Medicine, Auckland Hospital, Auckland, New Zealand.
authors.forename: Peter
authors.initials: P
authors.lastname: Browett
authors.affiliation: Department of Medicine, Middlemore Hospital, Auckland, New Zealand.
authors.forename: Hilary
authors.initials: H
authors.lastname: Blacklock
authors.affiliation: Department of Haematology, Gosford Hospital, North Gosford, NSW, Australia.
authors.forename: Cecily
authors.initials: C
authors.lastname: Forsyth
authors.affiliation: Department of Medicine, Border Medical Oncology, Albury-Wodonga, Vic., Australia.
authors.forename: Craig
authors.initials: C
authors.lastname: Underhill
authors.affiliation: Department of Medicine, Royal Perth Hospital, Perth, WA, Australia.
authors.forename: Paul
authors.initials: P
authors.lastname: Cannell
authors.affiliation: Department of Medicine, Concord Hospital, Concord, NSW, Australia.
authors.forename: Judith
authors.identifier: 0000-0001-8009-4593
authors.initials: J
authors.lastname: Trotman
authors.affiliation: Department of Medicine, Dunedin Hospital, Dunedin, New Zealand.
authors.forename: Annette
authors.initials: A
authors.lastname: Neylon
authors.affiliation: Faculty of Medicine, University of Melbourne, Victoria, Australia.|Haematology Service, Peter MacCallum Cancer Centre, Vic., Australia.
authors.forename: Simon
authors.initials: S
authors.lastname: Harrison
authors.affiliation: Centre for Biostatistics and Clinical Trials, Peter MacCallum Cancer Centre, Victoria, Vic., Australia.
authors.forename: Emma
authors.initials: E
authors.lastname: Link
authors.affiliation: Celgene Corporation, Summit, NJ, USA.
authors.forename: Arlene
authors.initials: A
authors.lastname: Swern
authors.affiliation: Centre for Biostatistics and Clinical Trials, Peter MacCallum Cancer Centre, Victoria, Vic., Australia.
authors.forename: Linda
authors.initials: L
authors.lastname: Cowan
authors.affiliation: Department of Clinical Therapeutics, University of Athens School of Medicine, Athens, Greece.
authors.forename: Meletios A
authors.initials: MA
authors.lastname: Dimopoulos
authors.affiliation: Faculty of Medicine, University of Melbourne, Victoria, Australia.|Haematology Service, Peter MacCallum Cancer Centre, Vic., Australia.
authors.forename: H
authors.initials: H
authors.lastname: Miles Prince
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D003907:Dexamethasone / Q000008:administration & dosage; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D000077269:Lenalidomide; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy*; D011379:Prognosis; D011446:Prospective Studies; D012008:Recurrence; D013792:Thalidomide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*
chemical_list: D020533:Angiogenesis Inhibitors; D013792:Thalidomide; D003907:Dexamethasone; D000077269:Lenalidomide
keywords: dose-attenuation; elderly; frail; lenalidomide; multiple myeloma