Long-term stabilisation of myeloma with curcumin

Long-term stabilisation of myeloma with curcumin

http://casereports.bmj.com/content/2017/bcr-2016-218148.full 
A small but significant number of myeloma patients consume dietary supplements in conjunction with conventional treatment primarily to help cope with the side effects of treatment, manage symptoms and enhance general well-being. Few, if any, use dietary supplementation as an alternative to standard antimyeloma therapy. Here, we describe a case in which curcumin has maintained long-term disease control in a multiply-relapsed myeloma patient. To the best of our knowledge, this is the first report in which curcumin has demonstrated an objective response in progressive disease in the absence of conventional treatment.

Curcumin is a polyphenol derived from the perennial herb Curcuma longa (turmeric) and has, for centuries, been used as a traditional Indian medicine. Several reports published over the two decades have claimed various health benefits of curcumin and this has led to its increasing popularity as a dietary supplement to prevent or treat a number of different diseases.5 ,6

The biological activity of curcumin is indeed remarkable. It is a highly pleiotropic molecule which possesses natural antioxidant, anti-inflammatory, antiseptic and analgesic properties.7 More recently, it has demonstrated antiproliferative effects in a wide variety of tumour cells including myeloma cells and exerts its antiproliferative effects through multiple cellular targets that regulate cell growth and survival.

In vitro, curcumin prevents myeloma cell proliferation through inhibition of IL-6-induced STAT-3 phosphorylation and through modulation of the expression of NF-kB-associated proteins such as IkB〈,Bcl-2, Bcl-xL, cyclin D1 and IL-68 and apoptosis-related molecules including p53 and Bax.9 In other studies, curcumin was shown to circumvent resistance to dexamethasone, doxorubicin and melphalan as well as potentiate the effects of bortezomib, thalidomide10 and lenalidomide.11 Furthermore, curcumin-induced cell death was not influenced by myeloma molecular heterogeneity.12

The antimyeloma effects of curcumin in the clinical setting however are less clear. Only one phase I/II study has evaluated curcumin treatment in myeloma patients. These patients were either asymptomatic, relapsed or had plateau phase disease. Treatment with curcumin downregulated the expression of NFkB, COX-2 and STAT3 in peripheral blood mononuclear cells, but no objective responses were observed in any subgroup of patients.13 This may be as a result of small sample size in this study, follow-up was limited to 3 months and clinical responses may have been observed with longer follow-up. However, downregulation of NFkB, COX-2 and STAT3 expression may not correlate with the clinical activity of curcumin and there may be further mechanisms of action that remain unclear, possibly through the modulation of another target. We would not be able to identify any patient-specific mechanisms of activity in this case study, as the patient has been taking curcumin for some time now and baseline bone marrow or peripheral blood samples are not available. However, in the setting of a clinical trial, it may be possible to use next-generation sequencing to help identify a mutation that may be a potential target for curcumin.

Another study examined its effects in preventing the progression of MGUS and smouldering myeloma to myeloma.14 ,15 The results showed that curcumin exerted a trace of biological activity with modest decreases in free light chain and paraprotein levels and a reduction in a marker of bone resorption with curcumin treatment, suggesting the therapeutic potential of curcumin in MGUS and smouldering myeloma. However, more studies are needed to address this further.

Whether such effects are observed in patients with active disease remains to be seen. The fact that our patient, who had advanced stage disease and was effectively salvaged while exclusively on curcumin, suggests a potential antimyeloma effect of curcumin. She continues to take daily curcumin and remains in a very satisfactory condition with good quality of life. This case provides further evidence of the potential benefit for curcumin in myeloma. We would recommend further evaluation of curcumin in myeloma patients in the context of a clinical trial.