Comment on: Monoclonal gammopathy of undetermined significance, smoldering multiple myeloma, and curcumin: A randomized, double‐blind placebo‐controlled crossover 4g study and an open‐label 8g extension study

Abstract

To the Editor: We read with interest the results of this clinical study by Golombick et al. [1]. This and two previous articles from the same authors show that in some, but not all patients with monoclonal gammopathies, the paraprotein load, urinary bone turnover, and the free light chain ratio (FLCr), prognostic factors for progression of disease, did moderately improve. Although the results are hopeful and the medico-scientific world looked forward to the recent follow-up of the previous studies, they also indicate that it is still unclear which criteria would allow to preselect responsive patients so that trials could become more meaningful. Curcumin had been chosen by the authors because of its capacity to down-regulate interleukin-6 (IL-6), an inflammatory cytokine, known to be associated to indicators of systemic inflammation such as C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR). Curcumin has been known for centuries in India as an anti-inflammatory compound and long-term curcumin intake significantly reduces CRP levels [2]. There is consequently reason to speculate that the observed response to curcumin might be associated to the presence of inflammation. This is especially true as inflammation-related microenvironmental factors may locally sustain ongoing lymphoproliferation and B cell transformation [3]. Regrettably, however, neither IL-6 nor CRP or ESR levels, associated to an unfavorable prognosis, have been reported. In case the authors are in the possession of data on IL-6, CRP, or ESR, it would be very easy to verify whether or not their results gain in statistical significance when the presence of inflammation at baseline is used as a patient selection criterion. Even if for none of these indicators data would be available, it might still be tempted to gain insight on the basis of existing results. Absolute levels of FLCs rather than their ratio have recently been suggested as potential biomarkers of immune stimulation and inflammation. CRP appears to be a most relevant indicator in acute illnesses. However, in cases where the CRP response is limited it appears associated to FLC levels [4]. Stratification of the available data according to the absolute levels of uninvolved FLCs (uFLCs) might, therefore, be used in an attempt to verify whether there is an association between the response of the three prognostic factors used to curcumin and the baseline level of uFLCs. If such an association is found and if the response of the three markers is coherent, uFLCs levels might serve as a criterion for patient selection in future trials on curcumin for monoclonal gammopathy of undetermined significance (MGUS) and thereby improve their statistical significance. Curcumin has given some hope to doctors and patients because it is relatively nontoxic in healthy people. Nevertheless, there are reasons for concern about safety in patients with monoclonal gammopathies [5]. As stated by the authors, curcumin may benefit some but not all patients with high risk MGUS. A rapid identification of the subgroup of patients who could benefit from curcumin treatment would be appreciated by all concerned. We, therefore, eagerly look forward to the above suggested further elaboration by the authors on the interesting results of their study [1]. Alphons J. M. Vermorken*, Jingjing Zhu*, Willem J. M. Van de Ven*, Emmanuel Andrès , * Department of Human Genetics, Laboratory for Molecular Oncology, KU Leuven, Belgium, Department of Internal Medicine, Diabetes and Metabolic Disorders, University Hospital of Strasbourg, Strasbourg, France.