A phase ii trial of thalidomide in the treatment of relapsed multiple myeloma (mm) with laboratory correlative studies

S. V. Rajkumar, R. Fonseca, A. Dispenzieri, M. Q. Lacy, S. Geyer, L. Wellik, S. Hayman, J. A. Lust, R. A. Kyle, P. R. Greipp, M. A. Gertz, T. E. Witzig

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16 Scopus citations


Aim: A phase II trial of thalidomide in relapsed MM with laboratory correlative studies examining bone marrow (BM) angiogenesis and plasma cell proliferation. Methods: 32 patients (pts), 22 male and 10 female, with relapsed MM were treated between April 1999 and July 2000. Thalidomide was given orally at a dose of 200 mg/day for 2 weeks, then increased as tolerated by 200 mg/day every 2 weeks, up to a maximum daily dose of 800 mg/day. Response was defined as a decrease in serum and urine monoclonal (M) protein by 50% or greater, and confirmed by repeat measurements at least 2 weeks apart. BM angiogenesis was studied in a blinded manner using immunohistochemical staining for CD34 to identify microvessels in 27 pts (84%). Microvessel density (MVD) was estimated by determining the average number of vessels in 3 hot spots examined at 400x magnification. Angiogenesis was also visually graded as low, intermediate and high. Plasma cell (PC) proliferation was studied using a slide based immunofluorescent bromodeoxyuridine incorporation assay (plasma cell labeling index; PCLI). Results: The median age was 67 years (range, 36-78). All pts had failed prior chemotherapy and 5 (16%) had failed stem cell transplantation. Response is still being evaluated, and currently 26 patients with at least two cycles of data are évaluable for response. 10 responses were confirmed, yielding a response rate of 38%. No complete responses were seen. Major grade 3 toxicities were sedation (10%) and neuropathy (10%). One pt each had grade 3 constipation, rash and vertigo. Pre-treatment MVD ranged 5-47 per 400x field (median 20). Angiogenesis grade was high in 52%, intermediate in 30%, and low in 18%. No significant changes were observed in MVD following treatment in 4 responders on whom at least 2 BM samples were available for study. Pre-treatment MVD and angiogenesis grade did not appear to be associated with response to therapy. Response rates were significantly higher in pts with a high PCLI (1) compared to those with a low PCLI, 57% versus 21%, respectively, (p=0.02). Conclusions: Thalidomide is effective in the treatment of relapsed MM with a response rate of 38% in this study. Its mechanism of action remains unclear. These results suggest that a high PCLI is a potential predictor of response to therapy.

Original languageEnglish (US)
Pages (from-to)168a
Issue number11 PART I
StatePublished - Dec 1 2000

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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