Thalidomide: evaluation of clinical parameters, cytokines, angiogenic markers, mast cells and marrow CD57+ cytotoxic T cells as outcome predictors

Mileshkin L, Honemann D, Gambell P, Trivett M, Hayakawa Y, Smyth M, Beshay V, Ritchie D, Simmons P, Milner AD, Zeldis JB, Prince HM.

Medical Oncologist Department of Haematology and Medical Oncology, Peter MacCallum Cancer Center, St Andrew’s Place, East Melbourne, VIC 3002, Australia. Linda.Mileshkin@petermac.org.

BACKGROUND AND OBJECTIVES In vitro studies suggest that thalidomide has an immunoregulatory role and alters the marrow microenvironment. We assessed laboratory and clinical parameters in patients with myeloma treated with thalidomide as potential prognostic markers and looked for changes with therapy.

DESIGN AND METHODS Seventy-five patients with relapsed/refractory myeloma received thalidomide in a phase II trial. Serial samples of platelet-poor plasma and bone marrow were tested for angiogenic cytokines including vascular endothelial growth factor (VEGF), marrow microvessel-density (MVD), mast cells and CD57+ cell expression. The effects of these parameters on response rate (RR), progression-free survival (PFS) and overall survival (OS) were analyzed.

RESULTS Elevated baseline VEGF predicted for a superior RR (p=0.018) and PFS. Elevated CD57+ cells also predicted superior PFS (p=0.012). MVD did not predict for RR, PFS or OS, but MVD and VEGF fell significantly in responders. Multivariate analysis identified that inferior OS was associated with age >65 years (p=0.017), raised lactate dehydrogenase (p=0.001), raised hepatocyte growth factor levels (p=0.012) and low pre-treatment CD57+ cells (p<0.001).>

INTERPRETATION AND CONCLUSIONS Our findings support the suggestion that thalidomide has anti-angiogenic and immunomodulatory effects in myeloma. The preferred method for assessing angiogenesis is plasma VEGF levels and the assessment of CD57+ cells for patients with myeloma receiving novel immunomodulatory drugs should be further investigated.

PMID: 17640854 [PubMed - as supplied by publisher]