Thalidomide for Patients With Relapsed Multiple Myeloma After High-Dose Chemotherapy and Stem Cell Transplantation: Results of an Open-Label Multicenter Phase 2 Study of Efficacy, Toxicity, and Biological Activity

• Published in: Mayo Clinic proceedings Vol. 79; no. 7; pp. 875 - 882
• Main Authors: Richardson, Paul, Schlossman, Robert, Jagannath, Sundar, Alsina, Melissa, Desikan, Raman, Blood, Emily, Weller, Edie, Mitsiades, Constantine, Hideshima, Teru, Davies, Faith, Doss, Deborah, Freeman, Andrea, Bosch, Joan, Patin, John, Knight, Robert, Zeldis, Jerome, Dalton, William, Anderson, Kenneth
• Format: Journal Article
• Language: English
• Published: Rochester, MN Elsevier Inc 01.07.2004; Mayo Medical Ventures; Elsevier Limited
• Subjects: Biological and medical sciences; Disease Progression; Disease-Free Survival; Female; General aspects; Hematologic and hematopoietic diseases; Humans; Immunodeficiencies. Immunoglobulinopathies; Immunoglobulinopathies; Immunopathology; Intercellular Adhesion Molecule-1 - blood; Interferon-gamma - blood; Interleukin-2 - blood; Interleukin-6 - blood; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Male; Medical sciences; Middle Aged; Multiple Myeloma - drug therapy; Multiple Myeloma - mortality; Multiple Myeloma - therapy; Prospective Studies; Recurrence; Stem Cell Transplantation; Thalidomide - administration & dosage; Thalidomide - therapeutic use; Thalidomide - toxicity; Tumor Necrosis Factor-alpha - analysis; Vascular Endothelial Growth Factor A - blood; MM; PR; IL; MR; SCT; CI; HDC; VEGF; BM; TNF; sICAM; IFN; CTC; PFS; Antineoplastic agent; Human; Immunopathology; Relapse; Toxicity; Stem cell; Multicenter study; Hematopoietic cell; Label; Malignant hemopathy; Myeloma; Biological activity; Multiple dose; Medicine; Chemotherapy; Treatment; Immunoglobulinopathy; Lymphoproliferative syndrome; Phase II trial; Graft; High dose; Thalidomide
• ISSN: 0025-6196; 1942-5546
• DOI: 10.4065/79.7.875

To determine the progression-free survival at 12 weeks, to evaluate the toxic effects, and to analyze the biological activity of thalidomide in patients with relapsed multiple myeloma (MM) after high-dose chemotherapy and stem cell transplantation. From 1999 to 2001, we performed a multicenter prospective phase 2 study in patients with MM that relapsed after high-dose chemotherapy and stem cell transplantation to evaluate the efficacy of oral thalidomide, with dose escalation from 200 to 600 mg/d over 12 weeks and a subsequent maintenance phase of 200 mg/d for up to 1 year. Outcome was correlated with serum and plasma levels of vascular endothelial growth factor and serum levels of tumor necrosis factor α, soluble intercellular adhesion molecule 1, interferon γ, interleukin (IL) 2, and IL-6 during treatment. Thirty patients were treated (19 men and 11 women; median age, 58 years). The median number of prior therapies was 5, and the median duration from diagnosis of MM to study enrollment was 4.3 years. The 12-week progression-free survival rate was 67% (95% confidence interval [CI], 48%-86%). The observed response rate (partial response plus minor response) was 43% (95% CI, 28%-60%) with a median duration of 6 months. Attributable toxicities included constipation, fatigue, rash, and neuropathy, which was dose limiting in 8 patients (27%). Dose escalation from 200 to 600 mg/d was achieved in 50% of patients. Although responses were observed with lower doses, possibly eliminating the need to escalate the dose, responses were also seen in patients who completed the dose escalation. Some patients had disease progression while receiving the maintenance dose of 200 mg/d. Analysis of biomarker assays did not identify any biomarker associated with greater response, but a significant increase in levels of soluble intercellular adhesion molecule 1, IL-2, and interferon γ was seen with thalidomide therapy. The optimal thalidomide dose varies, and adverse effects can be dose limiting. The dose of thalidomide therapy should be based on the individual patient to ensure that it is well tolerated and that a response is achieved.