Patients whose tumors exhibited MSI-H had a favorable prognosis, whereas those with 8p allelic imbalance had a poor prognosis; both alterations served as independent prognostic factors. To our knowledge, this is the first report of an association between 8p allelic imbalance and survival in patients with colorectal cancer.

clinicaltrials.gov identifier: NCT00635154.

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 5 22) and with (n 5 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 5 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,

Interleukin-1beta (IL-1beta) is abnormally expressed by the plasma cells obtained from myeloma patients, and it is a potent inducer of the important myeloma growth factor, IL-6. We investigated whether levels of IL-1beta biologic activity might distinguish different groups of patients with smoldering multiple myeloma (SMM). We measured the ability of IL-6 production by bone marrow stromal cells to serve as a surrogate marker for IL-1beta biologic activity. Using this IL-1beta bioassay, we found that it is sensitive at < 1 pg/ml of recombinant IL-1beta and that IL-1beta biologic activity is detectable with either mature or pro-IL-1beta-transduced myeloma cell lines. Patients with active myeloma induced quantitatively higher levels of stromal cell IL-6 production when compared with those with monoclonal gammopathy of undetermined significance (MGUS). The bioassay distinguished two groups of SMM patients, those who were high producers, similar to patients with active MM, and those who were low producers, comparable to MGUS patients. IL-1 antagonists inhibited the paracrine IL-6 production by > or = 90% in the majority of patients with an elevated IL-6 level. Based on such studies, it may be possible to predict patients that will progress to active MM and to delay or prevent this progression with IL-1 antagonists.

No abstract