A clinical and pharmacological study of arsenic trioxide in advanced multiple myeloma patients

Area of Science:

• Hematology
• Oncology
• Pharmacology

Background:

• Arsenic trioxide (ATO) and melarsoprol have demonstrated potential in inhibiting multiple myeloma (MM) cell growth in preclinical studies.
• This study investigates the clinical efficacy and toxicity of arsenic derivatives in patients with relapsed or refractory MM.

Purpose of the Study:

• To evaluate the safety and efficacy of arsenic trioxide (ATO) and melarsoprol in patients with relapsing or refractory secretory multiple myeloma (MM).
• To assess treatment response, toxicity profiles, and serum arsenic concentrations in MM patients receiving arsenic derivatives.

Main Methods:

• A clinical trial involving 12 patients with relapsing or refractory secretory MM.
• Ten patients received arsenic trioxide (ATO) (continuous or discontinuous schedule), and two received melarsoprol.
• Treatment response, adverse events, and serum arsenic levels were monitored.

Main Results:

• The melarsoprol arm was stopped early due to toxicity.
• Arsenic trioxide (ATO) treatment resulted in significant hepatic toxicity (grade 3 in one, grade 2 in eight patients) and other adverse events including neuropathy, encephalitis, and leuconeutropenia.
• No complete or partial remissions were observed; however, three patients showed a minor response and four had stable M-protein levels.
• Responses were transient after ATO discontinuation.

Conclusions:

• Arsenic trioxide (ATO) as a single agent did not yield significant responses in advanced MM patients, despite adequate arsenic exposure.
• The observed toxicities, particularly hepatic, limit its use.
• Improved strategies for drug delivery, pharmacokinetics, and combination therapies are necessary to enhance the efficacy of arsenic derivatives in MM treatment.