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Arsenic Trioxide: An Emerging Therapy for Multiple Myeloma

University of Arkansas for Medical Science, Little Rock, Arkansas, USA

Correspondence: Nikhil C. Munshi, M.D., Professor of Medicine, Section of Hematology/Oncology, University of Arkansas for Medical Science, 4301 W. Markham-Slot 776, ACRC Building, Suite 916, Little Rock, Arkansas 72205, USA. Telephone: (501) 686-8250; Fax: (501) 686-6442; e-mail: Munshinikhilc{at}exchange.uams.edu

Arsenic trioxide can inhibit proliferation and induce apoptosis in multiple myeloma (MM) cells in vitro and in vivo. In addition to affecting tumor growth, arsenic trioxide has been shown to inhibit angiogenesis, suggesting that it may have significant potency in the treatment of MM. Based on these observations, the clinical efficacy of arsenic trioxide was evaluated in patients with advanced refractory MM using a fixed-dose intravenous infusion given daily for a maximum of 60 days. Nine patients were evaluable. All nine had extensive prior therapy; seven had two or more high-dose chemotherapy cycles with autologous stem cell support. All nine patients had cytogenetic abnormalities, and six had chromosome 13 deletions. Of the four patients who completed more than 30 days of arsenic trioxide infusion, two had >50% reduction in myeloma paraprotein, one had stable disease, and one progressed. Of the five patients with <30 days infusion, two had stable disease and three progressed. Thus, on an intent-to-treat basis, two of nine (23%) patients responded (>50% paraprotein reduction). The regimen was well tolerated except for development of cytopenia, which responded to G-CSF, and a grade III pulmonary complication in one patient. In summary, arsenic trioxide has activity in end-stage, high-risk myeloma and deserves further evaluation in earlier-stage disease.

Key Words. . Arsenic trioxide • Multiple myeloma • Antiangiogenesis • Apoptosis

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