Abstract 4789

Patients with WM commonly display low cholesterol levels, particularly LDL and VLDL levels. Given these observations, we examined their levels in 110 patients with WM, and observed decreased total cholesterol (<160 mg/dL), LDL (<100 mg/dL) and VLDL (<40 mg/dL) levels in 41 (37.3%), 68 (61.8%) and 90 (81.8%) patients, respectively. Importantly, median serum IgM levels which serve as a surrogate marker for WM disease burden were higher among patients with hypocholesterolemia (3440 vs. 1587 mg/dL; p=0.0004). Longitudinal follow-up of progressing as well as responding patients demonstrated an inverse correlation between serum IgM and cholesterol levels, which was not an artifact of laboratory testing. Importantly, significantly lower serum IgM levels (885 vs. 1960 mg/dL; p=0.004) were observed among those patients who were on a statin lipid-lowering agent. We therefore investigated the in vitro potential of statins to mediate anti-WM activity and showed that simvastatin acted a potent inducer of WM cell apoptosis through inhibition of geranylgeranylated proteins. Given these observations, we investigated the potential of simvastatin to suppress disease progression in WM patients with slowly progressing disease who would otherwise have been on watch and wait.

Patients and Methods

Eighteen patients, 8 of whom were previously untreated, and who were asymptomatic with slowly progressing disease were enrolled in this study. The median age for these patients was 67 (range 42-88 years), median IgM was 2,610 (571-5,880 mg/dL), and median hematocrit was 35.4 (range 30.2-41.4%). Patients received Simvastatin at 20 mg daily for the first week, then dose escalated weekly by 20 mg a day to a maximum of 80 mg daily by week 4. Patients were maintained on therapy until progression.

Results

With a median follow-up of 6 months (range 3-18 months), 7 patients have demonstrated objective disease progression. No objective responses have been observed in any treated patients. Among non-progressing patients, serum IgM levels (2,610 vs. 2545 mg/dL) and hematocrit (35.4% vs. 34.5%) remain stable (p=NS). Grade 2 toxicities included elevation in CPK (n=1), and musculoskeletal pain (n=3). No grade 3 toxicities were observed.

Conclusions

Simvastatin does not produce objective responses in patients with WM, though may have potential for suppression of disease progression in some patients with WM.

Disclosures:

No relevant conflicts of interest to declare.

Topics:
cholesterol, statins, waldenstrom macroglobulinemia, immunoglobulin m, simvastatin, disease progression, follow-up, hypocholesterolemia, lipoproteins, vldl, loudness discomfort level

Author notes

*

Asterisk with author names denotes non-ASH members.

© 2009 by The American Society of Hematology
2009
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