Trisenox (Arsenic Trioxide) in the Treatment for Multiple Myeloma after Bone Marrow Transplantation.

Multiple myeloma (MM) remains an incurable disease, with median survival of 4–6 years despite various new therapeutic approaches including autologous and allogeneic bone marrow transplantation (BMT). New agents are studied and Arsenic Trioxide (ATO) seems to be a promising additional agent against progressive and refractory MM. Various mechanisms are described for the therapeutic effect of ATO: growth inhibition of myeloma cells; induction of apoptosis of drug resistant MM cell lines; inhibition of angiogenesis by blocking VEGF; interaction with BM microenvironment; immunologic mechanisms by a marked increase in lymphokine-activated Killer (LAK)-mediated killing and up-modulation of CD38 and CD54; inhibition of myeloma cells to stick to BM stromal cells by inhibiting IL-6. ATO is a form of arsenic, a naturally occurring element (As₂O₃), which was used for various therapeutic purposes for more than 2000 years. ATO was first approved by the FDA in 2000 for acute promyelocytic leukemia (APL), and is investigated for myelodysplastic syndrome (MDS) and other indications for ATO are currently under investigation.

We report our preliminary data from our clinical experience with ATO for 4 patients with MM after BMT, who had evidence of active and progressive disease. Other therapeutic approaches failed or were not relevant. ATO was given at low doses of 0.15 mg/kg/dose twice weekly and after respond at 0.3 mg/kg/dose once weekly. ATO was given intravenously in slow infusion over 2 hours together with intravenous lipids 500 ml (20%) to reduce ATO toxicity. ECG, markers for myeloma and possible adverse effects were monitored carefully. Oral ascorbic acid 500 mg twice daily was added to improve the effect of ATO. Our patients showed evidence of response to ATO both at the level of residual tumor mass and M-protein secretion. Furthermore, in one patient with severe GvHD we observed significant improvement of the GvHD manifestations concomittantly with Graft versus Myeloma effect.

Based on our data and the review of the literature regarding the use of ATO for MM, ATO might play in the future an established role in the treatment for MM. ATO might induce and augment immunomodulatory effects of Graft versus Myeloma. We discuss future research for the use of ATO in the treatment of MM.