Effect of thalidomide therapy on bone marrow angiogenesis in multiple myeloma

Abstract

Bone marrow (BM) angiogenesis is increased in multiple myeloma and is an important prognostic factor for survival. Previous studies have shown that BM angiogenesis does not change following chemotherapy or stem cell transplant. Given its potential antiangiogenic effect, we evaluated if thalidomide therapy would affect the BM microvessel density (MVD). We studied BM angiogenesis in 81 patients with various disease stages treated with thalidomide with or without dexamethasone. MVD was determined as previously described. MVD was compared between pretreatment marrows and those obtained 4-6 months following therapy. The median (range) MVD pretherapy was 28 (2-116) and post-therapy was 15 (3-97). A partial or complete response was seen in 58% of patients, stable disease in 41% and progressive disease in one patient. MVD decreased significantly in responders (median decrease of 12, Po0.001). In contrast, no significant change in MVD was seen in those failing to respond to thalidomide. Unlike the lack of resolution of angiogenesis reported with other therapies, we demonstrate for the first time a significant decrease in microvessels with thalidomide therapy. Although not conclusive, this result lends further support to the hypothesis that angiogenesis is a relevant therapeutic target in myeloma.

Patients with multiple myeloma treated with thalidomide: evaluation of clinical parameters, cytokines, angiogenic markers, mast cells and marrow CD57+ cytotoxic T cells as predictors of outcome

“…Thirdly, MVD and VEGF tended to decline in responding patients, confirming observations by some, but not all, investigators. [24][25][26] In support of our observation, Du et al and Hatjuharissi et al both reported a significant decline in MVD in patients with myeloma who responded to thalidomide and Kumar et al demonstrated a similar degree of MVD reduction to that seen in our study.…”

Dynamic Contrast-Enhanced Magnetic Resonance Imaging for Assessment of Antiangiogenic Treatment Effects in Multiple Myeloma

“…Increased bone marrow microcirculation is associated with adverse outcome in patients with multiple myeloma (4,5) as well as SMM (6), and angiogenesis is directly linked to the development of multiple myeloma-related bone disease (7,8). Furthermore, patients in remission after therapy showed a significantly decreased MVD compared with those with residual disease (9)(10)(11). In most of these studies, histologic evaluation of bone marrow biopsies was performed to quantify angiogenesis.…”

AKT activity regulates the ability of mTOR inhibitors to prevent angiogenesis and VEGF expression in multiple myeloma cells

“…The degree of angiogenesis inversely correlates with patient survival in disseminated myeloma (Rajkumar et al, 2000) as well as in solitary plasmacytomas of bone (Kumar et al, 2003). Furthermore, microvessel density (MVD) decreases significantly in MM patients responding to certain therapies but not in non-responders (Kumar et al, 2004). In myeloma, angiogenesis may be critical for the migration of tumor cells and their subsequent spread throughout the skeleton.…”