The clinical activity of arsenic trioxide, ascorbic acid, ifosfamide and prednisone combination therapy in patients with relapsed and refractory multiple myeloma

Abstract

This study aimed to investigate the activity of arsenic trioxide (As2O3) combined with ascorbic acid, ifosfamide, and prednisone chemotherapy in patients with repeatedly relapsed and refractory multiple myeloma (MM). Here, we retrospectively analyzed medical data of 30 MM patients showing progressive disease after receiving at least two previous lines of treatment including an immunomodulatory agent (thalidomide or lenalidomide) and a proteasome inhibitor. There were 19 men and eleven women, aged 54–73 (median 65) years, in this study. The distribution of different isotypes included immunoglobulin G(IgG) (12 patients), IgA (six patients), IgD (three), and light chain (nine patients). All the patients were Durie–Salmon stage III and had relapsed at least three times; the median cycles of prior therapies was 15 (range 10–18). The patients were treated with As2O3, ascorbic acid, and CP (ifosfamide 1 g on day 1, day 3, day 5, and day 7; prednisone 30 mg taken orally for 2 weeks). As2O3 was administered as an intravenous infusion at a dose of 10 mg/d and ascorbic acid at a dose of 2 g/d for 14 days of each 4-week cycle. The results showed that after 2 cycles of therapy, there were five patients that attained partial response, 15 had minimal response, five had no change, and five had progressive disease. The overall response rate was 66.7% (20/30 cases), 50% (10/20 cases), and 40% (2/5 cases), respectively, after 2, 4, and 6 cycles of the therapy. But there were no patients that attained complete remission. The median time of overall survival and progression-free survival were 48 (29–120) and 6 (2–8) months, respectively. The most common treatment-related adverse events included neutropenia, fatigue, anemia, thrombocytopenia, and infection that could be tolerated. The results showed that As2O3 combined with ascorbic acid, ifosfamide, and prednisone chemotherapy may be a choice treatment for repeatedly relapsed and refractory MM patients.

High-dose ascorbate and arsenic trioxide selectively kill acute myeloid leukemia and acute promyelocytic leukemia blasts in vitro

“…Our results are in keeping with the notion that both agents have favorable safety profiles in humans and do not induce significant myelosuppression. However, while low-dose ascorbate coupled to ATO has been used in pilot studies to treat AML [41] and multiple myeloma [42, 43], to the best of our knowledge no clinical studies combining ATO and high-dose ASC have been carried out in hematologic malignancies. Therefore, the presumed safety of the combination remains to be established in phase I studies.…”

Pharmacological dose ascorbic acid administration in relapsed refractory multiple myeloma patients

“…The overall response rate and median response duration were 74% and 17 months, respectively in this study. Other studies also reported synergistic effects of As 2 O 3 and AA combination in patients with RRMM [ 16 , 17 , 18 ]. As 2 O 3 and AA, in addition to bortezomib and dexamethasone combination can be an effective treatment strategy in these patients [19] .…”

The Protective Effects of Blue-Green Algae (Spirulina) Against Arsenic-Induced Differences in Lipid Panel and Hematological Parameters in Female Rats (Rattus norvegicus)

“…Previous studies have also reported a decline in hematological parameters in both animal models and human populations following exposure to toxicants [31]. Earlier research has reported that the decrease in Hb levels could be attributed to the inactivation of the δ-aminolevulinic acid dehydrase enzyme, which plays a crucial role in Hb production [32,33]. Furthermore, this reduction in Hb might be a result of the apoptosis of plasma cells induced by As [34].…”