title: Reduction in C-reactive protein indicates successful targeting of the IL-1/IL-6 axis resulting in improved survival in early stage multiple myeloma.
abstract: We report the long-term follow-up results of a phase II trial of IL-1 receptor antagonist and low-dose dexamethasone for early stage multiple myeloma (MM). Patients were eligible if they had smoldering multiple myeloma (SMM) or indolent multiple myeloma (IMM) without the need for immediate therapy. Forty seven patients were enrolled and subsequently treated with IL-1Ra; in 25/47 low-dose dexamethasone (20 mg weekly) was added. The primary endpoint was progression-free survival (PFS). In the clinical trial, three patients achieved a minor response (MR) to IL-1Ra alone; five patients a partial response (PR) and four patients an MR after addition of dexamethasone. Seven patients showed a decrease in the plasma cell labeling index (PCLI) which paralleled a decrease in the high sensitivity C-reactive protein (hs-CRP). The median PFS for the 47 patients was 1116 days (37.2 months). The median PFS for patients without (n = 22) and with (n = 25) a decrease in their baseline hs-CRP was 326 days (11 months) vs. 3139 days (104 months) respectively (P <0.0001). The median overall survival (OS) for the 47 patients was 3482 days (9.5 years). The median OS for patients without and with a decrease in their baseline hs-CRP was 2885 days (7.9 years) vs. median not reached, respectively (P = 0.001). In SMM/IMM patients at risk for progression to active myeloma, reduction in the hs-CRP indicates successful targeting of the IL-1/IL-6 axis resulting in improved PFS and OS. (Clinical Trials.gov Identifier: NCT00635154) Am. J. Hematol. 91:571-574, 2016. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, Minnesota.
authors.forename: John A
authors.initials: JA
authors.lastname: Lust
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Martha Q
authors.initials: MQ
authors.lastname: Lacy
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Steven R
authors.initials: SR
authors.lastname: Zeldenrust
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Witzig
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Laurie L
authors.initials: LL
authors.lastname: Moon-Tasson
authors.affiliation: Department of Medicine, University of Colorado, 12700 East 19th Ave, B168, Aurora, Colorado, 80045.
authors.forename: Charles A
authors.initials: CA
authors.lastname: Dinarello
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Donovan
mesh_terms: D002097:C-Reactive Protein / Q000187:drug effects / Q000378:metabolism*; D003907:Dexamethasone / Q000627:therapeutic use; D018572:Disease-Free Survival; D004359:Drug Therapy, Combination; D005500:Follow-Up Studies; D006801:Humans; D007136:Immunoglobulins / Q000097:blood; D053590:Interleukin 1 Receptor Antagonist Protein / Q000627:therapeutic use; D007375:Interleukin-1 / Q000037:antagonists & inhibitors*; D015850:Interleukin-6; D058990:Molecular Targeted Therapy / Q000379:methods; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000401:mortality; D016019:Survival Analysis
chemical_list: D007136:Immunoglobulins; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D015850:Interleukin-6; C009823:M-proteins (Myeloma); D003907:Dexamethasone; D002097:C-Reactive Protein