Prognostic Significance of Vitamin D Level in Patients with Multiple Myeloma

Background: Vitamin D is known to play an important role in bone mineral metabolism and it is also known to be associated with tumorigenesis and tumor immunity. Active form of vitamin D functions like a steroid hormone, binding to nuclear receptor and controlling cell proliferation, apoptosis and angiogenesis. Recently, number of studies have shown that vitamin D deficiency is associated with poor prognosis in many types of cancer including hematologic malignancies. One study suggests that vitamin D deficiency is correlated with poor overall survival in patients with multiple myeloma (MM) in white patients, but the differences was not observed in African Americans. In addition, the prognostic value of vitamin D in patients with multiple myeloma in Asian population remains unclear. In this study, we aimed to evaluate the prognostic value of vitamin D level in Korean MM patients.

Methods: Between September 2017 and May 2020, 129 patients were newly diagnosed with MM at Asan medical center, Seoul, South Korea. After excluding patients with no baseline vitamin D level, 98 patients were included in this analysis. Progression-free survival (PFS) was defined as time from date of diagnosis to disease progression or any cause of death, and overall survival (OS) was defined as time from the date of diagnosis to any cause of death. Key baseline characteristics and candidate prognostic factors including age, sex, European Cooperative Oncology Group Performance Status (ECOG PS), International staging stage (ISS), vitamin D were included in the univariate analysis. Vitamin D deficiency was defined as 25(OH) vitamin D level of < 10 mg/mL. In the multivariate analysis, variables which showed potential association with OS (p < 0.2) in the univariate analyses were included.

Results: Median age at diagnosis was 66.4 (range, 39 to 88), and 52 patients (53.1%) were male. Median 25(OH) Vitamin D level was 13.8 ng/mL (range, 1.1 to 91.0), and 36 patients (36.7%) had vitamin D deficiency. Higher proportion of patients in the vitamin D deficient group had ECOG PS ≥ 2 (50% vs 22.6%, p = 0.010), hemoglobin < 10g/dL (77.8% vs 46.8%, p = 0.005), albumin < 3.0 g/dL (69.4% vs 29.0%, p < 0.001), and CRP > 0.3 mg/dL (69.4% vs 33.9%, p = 0.001) compared with non-vitamin D deficient group. Presence of bone lesions was higher in the vitamin D deficient group (86.1% vs 75.8%, p = 0.025), but there was no statistical difference in terms of number of bone lesion and prevalence of pathologic fracture between two groups.

With median follow-up duration of 27.9 months (95% Confidence interval [CI], 13.2 to 42.8), 2-year PFS and OS rate in entire patients were 42.9% (95% CI, 34.1 to 53.9) and 64.3% (95% CI, 55.5 to 74.5), respectively. Patients in the vitamin D deficient group was significantly associated with worse PFS (2-year PFS 44.8% vs 66.9%, p = 0.008) and OS (2-year OS 47.2% vs 74.2%, p = 0.024) compared with the non-vitamin D deficient group. In the univariate analysis, vitamin D deficiency showed potential association with both PFS and OS (p < 0.2) along with age, sex, and ISS stage. In the multivariate analysis, vitamin D deficiency was independently associated with both poor PFS (Hazard ratio [HR], 2.00; 95% CI, 1.07 to 3.75, p = 0.031) and OS (HR, 1.86; 95% CI, 1.01 to 3.46, p= 0.050).

In vitamin D deficient group (n = 36), 27 patients (75%) received vitamin D supplementation. Patients with vitamin D supplementation showed trend towards better OS compared with non-vitamin D supplementation group, with 2-year OS rate of 51.9% vs 33.3% (p = 0.140), respectively.

Conclusion: Our results demonstrated the prognostic value of vitamin D deficiency in Korean MM patients. Although this study was conducted in a single center, this study is meaningful as it is the first study to evaluate the prognostic value of vitamin D levels in patients of the Asian population.

Yoon:Celltrion: Honoraria, Research Funding; Sanofi: Research Funding; Boryung: Honoraria, Research Funding; Beigene: Research Funding; Samyang: Honoraria, Research Funding; Amgen: Honoraria; Takeda: Honoraria; BMS: Honoraria; Novartis: Honoraria; GSK: Honoraria; GI Cell: Consultancy; Ab Clone: Consultancy; Pharos iBio: Consultancy; Janssen: Honoraria, Research Funding; Kirin: Honoraria, Research Funding; Roche: Honoraria.