title: Seven-year median time to progression with thalidomide for smoldering myeloma: partial response identifies subset requiring earlier salvage therapy for symptomatic disease.
abstract: Smoldering multiple myeloma (SMM) is usually followed expectantly without therapy. We conducted a phase 2 trial in 76 eligible patients with SMM, combining thalidomide (THAL, 200 mg/d) with monthly pamidronate. In the first 2 years, THAL dose reduction was required in 86% and drug was discontinued in 50%. Within 4 years, 63% improved, including 25% qualifying for partial response (PR); by then, 34 patients had progressed and 17 required salvage therapy. Unexpectedly, attaining PR status was associated with a shorter time to salvage therapy for disease progression (P < .001), perhaps reflecting greater drug sensitivity of more aggressive disease. Low beta-2-microglobulin levels less than 2 mg/L were independently associated with superior overall and event-free survival. Four-year survival and event-free survival estimates of 91% and 60%, respectively, together with a median postsalvage therapy survival of more than 5 years justify the conduct of a prospective randomized clinical trial to determine the clinical value of preemptive therapy in SMM. Trial registered at http://www.clinicaltrials.gov under identifier NCT00083382.
authors.affiliation: Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, USA.
authors.forename: Bart
authors.initials: B
authors.lastname: Barlogie
authors.forename: Frits
authors.initials: F
authors.lastname: van Rhee
authors.forename: John D
authors.initials: JD
authors.lastname: Shaughnessy
authors.forename: Joshua
authors.initials: J
authors.lastname: Epstein
authors.forename: Shmuel
authors.initials: S
authors.lastname: Yaccoby
authors.forename: Mauricio
authors.initials: M
authors.lastname: Pineda-Roman
authors.forename: Klaus
authors.initials: K
authors.lastname: Hollmig
authors.forename: Yazan
authors.initials: Y
authors.lastname: Alsayed
authors.forename: Antje
authors.initials: A
authors.lastname: Hoering
authors.forename: Jackie
authors.initials: J
authors.lastname: Szymonifka
authors.forename: Elias
authors.initials: E
authors.lastname: Anaissie
authors.forename: Nathan
authors.initials: N
authors.lastname: Petty
authors.forename: Naveen S
authors.initials: NS
authors.lastname: Kumar
authors.forename: Geetika
authors.initials: G
authors.lastname: Srivastava
authors.forename: Bonnie
authors.initials: B
authors.lastname: Jenkins
authors.forename: John
authors.initials: J
authors.lastname: Crowley
authors.forename: Jerome B
authors.initials: JB
authors.lastname: Zeldis
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001853:Bone Marrow / Q000473:pathology*; D004164:Diphosphonates / Q000008:administration & dosage*; D018450:Disease Progression; D018572:Disease-Free Survival; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000517:prevention & control*; D015999:Multivariate Analysis; D000077268:Pamidronate; D011230:Precancerous Conditions / Q000188:drug therapy*; D016879:Salvage Therapy; D013792:Thalidomide / Q000008:administration & dosage*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D004164:Diphosphonates; D007166:Immunosuppressive Agents; D013792:Thalidomide; D000077268:Pamidronate