Haematologica, Vol 92, Issue 8, 1075-1082 doi:10.3324/haematol.11208
Copyright © 2007 by Ferrata Storti Foundation
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Multiple 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

Linda Mileshkin, Dirk Honemann, Peter Gambell, Melanie Trivett, Yoshihiro Hayakawa, Mark Smyth, Victoria Beshay, David Ritchie, Paul Simmons, Alvin D. Milner, Jerome B. Zeldis, H. Miles Prince

From the Division of Haematology and Medical Oncology, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia (LM, DH, PG, MT, DR, PS, HMP); Tumour Immunology Laboratory, Division of Research, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia (DH, YH, VB, DR, HMP); University of Melbourne, Parkville, Victoria, Australia (LM, MS, DR, PS, HMP); Centre for Biostatistics and Clinical Trials, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia (ADM); Celgene Corporation, New Jersey, USA (JBZ)

Correspondence: Linda Mileshkin, Medical Oncologist Department of Haematology and Medical Oncology, Peter MacCallum Cancer Center, St Andrew’s Place, East Melbourne, VIC 3002, Australia. E-mail: Linda.Mileshkin{at}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.

Key words: myeloma, thalidomide, angiogenesis, CD57, prognosis, VEGF.




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[Abstract] [Full Text] [PDF]