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www.sciedu.ca/jhm Journal of Hematological Malignancies, 2013, Vol. 3, No.1
ISSN 1925-4024 E-ISSN 1925-4032
18
CASE REPORT
Long term use of curcumin in two smoldering multiple
myeloma patients
Terry Golombick1, Terrence H. Diamond1, Arumugam Manoharan2, Rajeev Ramakrishna2
1. Department of Endocrinology, St George Hospital, Sydney, Australia. 2. Southern Sydney Haematology, University of
Wollongong, NSW, Australia.
Correspondence: Terry Golombick. Address: Prichard Wing, St George Hospital, Kogarah, NSW, Australia, 2217. Email:
terry.golombick@sesiahs.health.nsw.gov.au
Received: November 13, 2012 Accepted: January 24, 2013 Online Published: February 18, 2013
DOI: 10.5430/jhm.v3n1p18 URL: http://dx.doi.org/10.5430/jhm.v3n1p18
Abstract
Introduction: Smoldering Multiple Myeloma (SMM) is an asymptomatic plasma cell disorder which has an overall risk
of progression to multiple myeloma of 10% per year. The cornerstone of managing SMM is a “watch and wait” strategy.
Curcumin has been shown to improve disease status in some patients with MGUS and SMM and has been added to the
mainstream treatment of myeloma patients. We report here for the first time on long term use of oral curcumin in 2 SMM
patients.
Patients: Two male Caucasian patients over the age of 40 presented to their general practitioners with fatigue/shoulder
pain. Blood tests revealed paraproteinemia and a diagnosis of SMM was made based on IMWG guidelines. Both were
entered into a 9 month clinical trial of oral curcumin in patients with plasma cell dyscrasias. Thereafter, they elected to
continue on the same regimen of oral curcumin, for a period of 2 years.
Results/Discussion: Both patients showed continued improvement in a number of markers of disease activity including
serum free light chains, paraprotein and % plasma cells in the bone marrow. These results suggest that patients with
smoldering myeloma may benefit from daily ingestion of curcumin and long term use does not result in toxicity.
Key words
Smoldering Multiple Myeloma, Monoclonal Gammopathy of Undetermined Significance, Curcumin
1 Introduction
Smoldering Multiple Myeloma (SMM) is an asymptomatic plasma cell disorder which has an overall risk of progression to
multiple myeloma of 10% per year for the first 5 years. This diminishes gradually thereafter. SMM is a more advanced
pre-malignant condition than monoclonal gammopathy of undetermined significance (MGUS).The cornerstone of
managing SMM is a “watch and wait” strategy [1]. Although it is currently not possible to predict the clinical course of
SMM, features predicting patients at highest risk include the size and type of M-protein, with IgA having a higher risk
compared to IgG paraprotein, % plasma cell dyscrasia, and an abnormal serum-free light chain ratio.
www.sciedu.ca/jhm Journal of Hematological Malignancies, 2013, Vol. 3, No. 1
Published by Sciedu Press 19
Given the uncertainty of disease progression with SMM, early intervention aimed at reducing the abnormal protein load,
the abnormal serum-free light chain ratio and the % plasma cell load would be of benefit to the patient. It would be
essential that this preventative approach does not itself increase the risk of progression or result in toxicity. Curcuma longa
(turmeric) is a perennial herb belonging to the ginger family. The most active component in turmeric is curcumin [2]. Based
on its demonstrated anti-myeloma cell activity, both in vitro and in vivo [3, 4], we have carried out both a 6 month pilot
study [5] and a 6 month randomised, double-blind placebo-controlled cross-over 4g study and a 3 month open-label 8g
extension study [6] and shown that oral curcumin can, in a select group of MGUS and SMM patients, decrease free light
chains (rFLC, dFLC and iFLC), paraprotein and bone resorption. Here, we present a report of two patients with SMM who
were recruited into our second study [6] and who elected to continue on the same regimen of oral curcumin daily after the
study.
2 Case presentations
Patient 1: A 47 year old male presented to his GP in 2010 with a 3 month history of fatigue. Routine blood tests showed an
IgG kappa paraprotein of 29.7g/L, 33% plasma cells in the bone marrow and a free light chain ratio (rFLC) of 26.77 (K =
97.7 mg/L; L = 3.65 mg/L). Renal function and calcium levels were normal.
Patient 2: A 66 year old male whose disease was diagnosed in 2010 because of an unusual acromio-clavicular septic
arthritis. Blood tests revealed an IgG lambda paraprotein of 31.7g/L, 7% plasma cells in the bone marrow and rFLC of 0.3
(K = 15.7 mg/L; L = 53.2 mg/L). Renal function and calcium levels were normal.
Table 1. Clinical data of patients 1 and 2 at baseline, 9 months and at 2 years of curcumin therapy
Variable 1. Baseline 1. 9 months 1. 2 years 2.Baseline 2. 9 months 2. 2 years
age (years) 47 48 49 66 67 68
% plasma cells 33 15 7 2
Paraprotein (g/L) 29.7 26.6 24.4 31.7 27.7 23.6
Free light chain ratio (0.3-1.7) 26.77 14.37 4.5 0.3 0.22 0.4
dFLC (mg/L) 94.1 137.7 125.4 37.5 37.9 46
iFLC (mg/L) 97.7 148 161 53.2 48.6 71.6
uiFLC 3.65 10.3 35.6 15.7 10.7 25.6
Globulin (22-38 g/L) 47 40 39 53 48 51
Gamma globulin (7-16g/L) 32.8 28.3 26.4 34.8 31.8 28.2
Ig G (6.2-14.4g/L) 44.25 38.8 39.47 49.03 41.62 44.12
Ig M (0.48-3.04g/L) 0.23 0.23 0.2 0.62 0.45 0.5
Ig A (0.6-3.96g/L) 0.12 0.12 0.12 1.15 1.36 1.55
CD3 T cell (%) 81 72 63 76 75 76
CD4 T helper cell (%) 48 41 30 40 44 47
CD8 cytotoxic T cell (%) 29 26 26 29 27 31
Total protein (64-83g/L) 95 84 84 92 86 84
25-OH Vitamin D (nmol/L) 153 158
Based on the IMWG classification system, these two patients were diagnosed with SMM. They were entered into our 6
month randomised, double-blind placebo-controlled cross-over 4g study and 3 month open-label 8g extension study of
oral curcumin. After 9 months of curcumin therapy, both patients demonstrated an improvement in paraprotein, rFLC,
iFLC, uiFLC, total protein, as well as decreases in their elevated IgG, globulin and gamma globulin levels (see Table 1).
Based on their overall clinical improvement, they elected to continue with curcumin therapy after completion of the
clinical trial on a maintenance dose of 6g/day. Follow up blood tests and a bone marrow biopsy were performed after 2
years of curcumin therapy in order to determine whether the curcumin had altered the disease progression.
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www.sciedu.ca/jhm Journal of Hematological Malignancies, 2013, Vol. 3, No.1
ISSN 1925-4024 E-ISSN 1925-4032
22
To further determine the effect of curcumin on immune function, we re-looked at and analysed the data from our previous
randomised study [6]. Eighteen (of 25) patients completed the 9 month study (ie 6 months of 4g and 3 months of 8g
curcumin). All 18 patients had IgG plasma cell dyscrasias. Analysis of surface leucocyte antigen characterisation and
immunoglobulin level data from baseline till 9 months showed that in 18 patients there was no mean change in percentage
distribution of CD3 T cells, CD4 T helper cells and CD8 cytotoxic T cells (see Table 2) over 9 months of curcumin
therapy. There was no change in IgA, however, there was a decrease in IgM (P=0.04) from baseline till 9 months (see
Table 2).
3 Discussion
We describe the effects of 2-years of curcumin therapy on two SMM patients, one of these (ie patient 1) at high risk of
transformation to multiple myeloma. Both these patients showed a continued improvement in several markers of their
disease activity and in particular, a decrease in % plasma cells in the bone marrow. These data are in accordance with our
previous findings [5, 6]. Although myeloma is a “patchy” disease, the bone histopathology failed to demonstrate progression
of the disease, but suggested an improvement in the plasma cell infiltrate.
The mechanism(s) by which curcumin slows down the disease activity in plasma cell dyscrasias is unclear. Previous
studies have identified down-regulation of interleukin-6 (a growth factor for myeloma and also an inflammatory cytokine)
and suppression of receptor activator of nuclear factor kappa-B ligand (RANKL) signaling as two possibilities [2-4, 8]. In
their recent review [9], Vermorken et al have attributed the beneficial effect of curcumin to its potential anti-inflammatory
action. They also expressed concerns about the possible immunosuppressive effects of curcumin and its effects on cellular
immunity. Our experience to date does not substantiate these concerns. A detailed analysis of immune function in 18
patients who had previously been studied and treated with curcumin for 9 months (see Table 2) did not show significant
changes in the number of T-cell (CD3, CD4 and CD8) subsets. These findings can now be extended to 2 years as shown in
Patients 1 and 2. Neither of these patients had any clinical events attributable to immunosuppression (infections,
progression to myeloma or development of a second malignancy). Furthermore, neither patient displayed any side-effects
from long term, high dose curcumin therapy and neither has developed skeletal events that require bisphosphanate therapy.
Our results are encouraging, but the exact role and place of curcumin for patients with monoclonal gammopathies and
SMM will need to be determined by large scale, multi-centre studies.
References
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