The Majority of Myeloma Patients Are Vitamin D Deficient, Unrelated to Survival or Cytogenetics

Abstract

Introduction: Since a link between solar radiation, vitamin D production, and decreased colon cancer mortality was established in 1980, there has been increasing interest in vitamin D and cancer, suggesting that higher vitamin D levels improve overall survival, specifically in breast and colorectal cancer (Maalmi H et al, Eur J Canc, May-2014, PMID 24582912), but also in follicular lymphoma (Kelly JL, J Clin Onc, 1-May-2015, PMID 25823738). In myeloma, largest published series is from the Mayo Clinic reporting on 148 newly diagnosed MM patients for which no survival association was found, but there were associations between low 25-OH-Vit D (<20 ng/mL) and higher serum CRP, serum creatinine, and ISS stage (Ng AC, Am J. Heme, Jul-2009, PMID 19415724); we wanted to expand on their trailblazing analysis. Cytogenetically high risk myeloma characterized by the amplification of 1q21 is associated with increased serum levels of soluble IL-6 receptor (sIL-6r) (Stephens OW, Blood, 2012, PMID 22072558) which may be associated with other markers of inflammation, e.g. CRP, creatinine, and b2microglobulin. Methods: The Buckeye Myeloma Registry (OSU 10115) opened in 2011 to enroll any patient with a plasma cell dyscrasia. Serum total 25-OH-Vitamin D was measured at the time of the initial clinic visit to the myeloma group at Ohio State. Results: Of a total of 843 patients, 115 (13.6%), 53 (6.3%) with SMM, and 675 (80.1%) with MM. In the 675 MM patients, the median age was 64 y.o. (range 28-95), 14.5% African-American and the remainder Caucasian, with 28.6% ISS stage 1, 48.7% ISS stage 2, 21.9% ISS stage 3, and 24.5% unknown. At diagnosis for the MM patients, 67% presented with lytic bone disease. Out of 675 MM patients, there were 52 (7.7%) patients with < 10 ng/mL 25-OH-Vit D, 394 (51%) with low vit D (10-30 ng/mL), and 229 (39%) for 25-OH-Vit D 30-100 ng/mL. There was no correlation between 25-OH-Vit D and BMI or creatinine, but there was a strong correlation with race (r=0.18, p<0.000026). Among the MM patients, log-rank [Mantel-Cox] analysis of overall survival with serum 25-OH-Vit D including all groups demonstrated no significant differences (p=0.9725) with only 101 events. There was no correlation between 25-OH-Vit D and the presence on CD138-selected FISH of 1q21 amplification (p=0.196), 17p (p53) deletion (p=0.68), or 13q deletion (p=0.812). Conclusion: The majority of myeloma patients are vitamin D deficient, but this was not associated with worsened overall survival or with high risk cytogenetics. Cox proportional hazards analyses of survival adjusted for significant univariate covariates will be presented at the meeting. Correlations with presence or absence of diffuse lytic bone disease, severity of renal insufficiency, and race will also be presented at the meeting. Disclosures No relevant conflicts of interest to declare.

Impact of vitamin D level at diagnosis and transplantation on the prognosis of hematological malignancy: a meta-analysis

“…A flow diagram of the article selection process is shown in Figure 1. 22 articles were excluded with the following reasons: (1) duplicate publications from overlapping cohort 47,48 , (2) insufficient data of primary endpoint [49][50][51][52][53][54][55][56][57][58][59][60] , and (3) transplantations including many non-malignancies or unidentified diseases [61][62][63][64][65][66][67][68] . The characteristics of each study are summarized in Table I.…”

Vitamin D deficiency linked to abnormal bone and lipid metabolism predicts high-risk multiple myeloma with poorer prognosis

“…Recent clinical studies have revealed a consistent and strong association between vitamin D status and tumor progression and survival in several solid tumor ( 7 ). Vitamin D deficiency is extremely common in patients with multiple myeloma (MM), however, data on the association between vitamin D status and clinical outcomes of newly diagnosed multiple myeloma (NDMM) are rather inconsistent ( 8 – 12 ). There was a study showing vitamin D deficiency in NDMM is unrelated to survival or cytogenetics ( 12 ).…”

Reviewing the Significance of Vitamin D Substitution in Monoclonal Gammopathies

“…Similarly, in 2015, researchers reported that increased plasma cells in BM are correlated with VitD levels < 10 ng mL –1 [ 95 ]. In MM patients, most of whom lack vitamin D [ 96 ], this correlation was also valid in a long-term follow-up study, where the risk of progression, development of MBD and osteoporosis, and all-cause mortality was low in patients with adequate VitD levels (>75 nmol L −1 ) [ 97 ]. Moreover, in these patients, VitD analogues have been shown to promote cell cycle arrest [ 88 , 98 ].…”