• John A Lust, Martha Q Lacy, Steven R Zeldenrust, Angela Dispenzieri, Morie A Gertz, Thomas E Witzig, Shaji Kumar, Suzanne R Hayman, Stephen J Russell, Francis K Buadi, Susan M Geyer, Megan E Campbell, Robert A Kyle, S Vincent Rajkumar, Philip R Greipp, Michael P Kline, Yuning Xiong, Laurie L Moon-Tasson, and Kathleen A Donovan.
• Division of Hematology, Mayo Clinic, Rochester, MN 55905. lust.john@mayo.edu
• Mayo Clin. Proc. 2009 Feb 1; 84 (2): 114122114-22.

ObjectiveTo conduct in vitro studies as well as a phase 2 clinical trial in patients with smoldering or indolent multiple myeloma to determine if interleukin 1 (IL-1) inhibitors can delay or prevent active myeloma.Patients And MethodsStromal cells were cocultured with IL-1beta-expressing myeloma cells in the presence of dexamethasone, IL-1 receptor antagonist (IL-1Ra), or both. Levels of interleukin 6 (IL-6) and of apoptosis were also quantified. Between November 19, 2002, and May 24, 2007, 47 patients were enrolled in the study and subsequently treated with IL-1Ra. In 25 (53%) of the 47 study patients, low-dose dexamethasone (20 mg/wk) was added. The primary end point was progression-free survival (PFS).ResultsIn vitro, IL-1Ra was superior to dexamethasone at inhibiting IL-6 production; maximal IL-6 inhibition and apoptosis induction were achieved by addition of both IL-1Ra and dexamethasone. In the clinical trial, 3 patients achieved a minor response to IL-1Ra alone; 5 patients achieved a partial response and 4 patients a minor response after addition of dexamethasone. Seven patients showed a decrease in the plasma cell labeling index that paralleled a decrease in high-sensitivity C-reactive protein (hs-CRP) levels. The median overall PFS was 37.5 months. The median PFS for patients without (n=12) or with (n=35) a greater than 15% decrease in 6-month vs baseline hs-CRP levels was 6 months and more than 3 years, respectively (P=.002). Disease stability was maintained in 8 patients who received therapy for more than 4 years.ConclusionIn patients with smoldering or indolent multiple myeloma who were at risk of progression to active myeloma, treatment with IL-1 inhibitors decreased the myeloma proliferative rate and hs-CRP levels in those who responded, leading to a chronic disease state and an improved PFS.Trial Registrationclinicaltrials.gov identifier: NCT00635154.

37 keywords...

hide…