Immune dysregulation and alteration of the bone marrow microenvironment allowing plasma cells to escape immune surveillance are well-known factors associated with the proliferation of clonal plasma cells and development of multiple myeloma (MM). Whilst immunotherapeutic approaches are now commonplace in a wide spectrum of malignancies, this aberration of myeloma development gives rise to the biological rationale for the use of immune checkpoint inhibitors (ICIs) in MM. However, the initial experience with these agents has been challenging with limited single agent efficacy, significant toxicity, and side effects. Herein, we review the biological and immunological aspects of MM and ICIs. We discuss the basic biology of immune checkpoint inhibitors, mechanisms of resistance, and drug failure patterns, review the published clinical trial data for ICIs in MM, and look towards the future of ICIs for MM treatment.

1534 Background: In the United States cancer is the second leading cause of mortality, as such, primary prevention of cancer is a major public health concern. Vitamin D supplementation has been studied as a primary prevention method for multiple diseases including cardiovascular disease, osteoporosis, diabetes mellitus and cancer. The role of aspirin as primary prevention of cancer is still controversial. With fast emergence of large randomized controlled trials (RCTs) in that regards, we aimed to evaluate the efficacy of Vitamin D supplementation as primary prophylaxis for cancer. Methods: A comprehensive electronic database search was conducted for all RCTs where comparison of Vitamin D supplementation versus placebo for the prevention of any type of disease with at least 3 years of Vitamin D supplementation was used and where cancer incidence or mortality was reported. The primary outcome was cancer-related mortality and cancer incidence. We calculated risk ratios (RRs) and 95% confidence intervals (CIs) using a random-effects model at the longest follow-up. Results: We included 10 RCTs with 79,055 total patients, mean age of 68.07 years, a female percentage of 78.02% and a minimum follow-up of 4 years and more. Vitamin D was associated with significant reduction of cancer-related mortality compared with placebo (RR 0.87; 95% CI: 0.79-0.96; P = 0.05: I2= 0%). Compared with placebo, Vitamin D was not associated with significant reduction of cancer incidence (RR: 0.96; 95% CI: 0.86-1.07; P = 0.46; I2= 31%). Conclusions: Our study highlights that the use of Vitamin D supplementation for primary prevention of cancer is important as it does decrease cancer-related mortality once cancer is diagnosed, however it has no role or effect on cancer incidence.

Background: PARP (poly(ADP-ribose) polymerase) inhibitors are used more frequently in platinum-sensitive recurrent ovarian cancer. Methods: We conducted a meta-analysis to check the strength of evidence on the use of PARP inhibitors for relapsed platinum-sensitive ovarian tumors. Results: A total of 4 randomized controlled trials were included in our analysis with a total of 1,264 patients (PARP n = 780). Progression-free survival (PFS) was significantly better in the PARP group in BRCA-positive patients (hazard ratio (HR) 0.24, 95% confidence interval (CI) 0.19-0.30; p < 0.00001). PFS was significantly better in the PARP group in BRCA-negative patients (HR 0.52, 95% CI 0.36-0.75; p < 0.00001). Similarly, we found a significant difference in overall survival (OS) between the two groups in BRCA-positive patients (HR 0.72, 95% CI 0.53-0.97, p= 0.03). Conclusion: PARP inhibitors in addition to standard platinum-based regimens along with subsequent maintenance therapy significantly improves PFS and OS with an acceptable side-effect profile in BRCA-positive women with recurrent, previously platinum-sensitive HGSOC.