Retrospective analysis of the relationship between time to anti-resorptive therapy and incidence of skeletal related events in patients with multiple myeloma.
Authors: Binder Adam F , Hughes Kelly , Abdulkareem Abdullateef , Barsouk Adam , Raj Niketa , Zhan Tingting , Gundepalli Sai , Devarakonda Srinivas S. 
Published: June 2023

8048

Background: Patients with multiple myeloma (MM) often have bone disease at diagnosis and are at risk of developing skeletal related events (SRE) (pathological fractures, spinal cord compression, and/or need for radiotherapy or surgery to bone). It is well established that for patients with lytic bone lesions at diagnosis, the use of anti-resorptive agents lead to a lower incidence of SREs. However, it is common for initiation of anti-resorptive therapy to be delayed. Recent studies have demonstrated that anti-resorptive therapy is underutilized in patients with MM. However, the effect of time to initiation of anti-resorptive agent after diagnosis of MM on SREs has not been well studied. Herein, we conducted a multi-center retrospective analysis to determine if time to anti-resorptive agent has an adverse impact on the risk of SREs. Methods: We performed a retrospective cohort study using our Electronic Health Record system to identify patients with newly diagnosed MM between July 1st, 2016 and June 30th, 2019 at two large academic centers. Patients previously treated or patients not treated with anti-resorptive therapy were excluded. The study’s primary endpoint was hazard ratio of developing a SRE based on time to anti-resorptive therapy. The relationship between incidence of SREs and time to anti-resorptive therapy, gender, age, International Staging System (ISS) stage at diagnosis, and prior SRE present at diagnosis was analyzed by using a multivariable Cox proportional hazards model. The cutoff point of anti-resorptive therapy delay was based on the recursive partitioning of univariable Cox model. Results: 759 patients were included in the study (Thomas Jefferson University: n = 232; The Ohio State University: n = 527). Median age at diagnosis is 60.2 years (IQR: 12.4 years). 57% of patients were male. 77.9% and 20.3% of patients identified as white and black respectively. 210 patients (27.7%) were noted to have osteopenia, 45 (5.9%) had osteoporosis, 229 (30.2%) were vitamin D deficient, and 319 (42%) were obese at diagnosis. A skeletal related event was present at diagnosis in 338 (45.1%) of patients. 180 (34%) patients received anti-resorptive agents within 31 days. A delay in initiating anti-resorptive agents of greater than 31 days from diagnosis had an increased risk for SRE with a hazard ratio 1.654 (1.054~2.598; p-value: 0.029). Conclusions: This large multicenter retrospective study demonstrated that time to anti-resorptive therapy MM patients has a significant impact on the risk of SRE. Given many of the challenges in starting anti-resorptive therapy in a timely manner, this study emphasizes the need for inter-professional, multi-disciplinary collaborations to streamline the workflow and start therapy within the first month of diagnosis. Ongoing efforts are underway to develop quality improvement processes to achieve this goal.