Adherence and cumulative bisphosphonate dose in relation to risk of skeletal-related events among older patients with multiple myeloma.

person Jifang Zhou University of Illinois at Chicago, Department of Pharmacy Systems, Outcomes and Policy, Chicago, IL info_outline Jifang Zhou, Karen Sweiss, Pritesh Rajni Patel, Edith Nutescu, Naomi Ko, Brian C-H Chiu, Gregory Sampang Calip

Authors person Jifang Zhou University of Illinois at Chicago, Department of Pharmacy Systems, Outcomes and Policy, Chicago, IL info_outline Jifang Zhou, Karen Sweiss, Pritesh Rajni Patel, Edith Nutescu, Naomi Ko, Brian C-H Chiu, Gregory Sampang Calip Organizations University of Illinois at Chicago, Department of Pharmacy Systems, Outcomes and Policy, Chicago, IL, University of Illinois at Chicago, Department of Pharmacy Practice, Chicago, IL, University of Illinois at Chicago, Department of Medicine, Division of Hematology and Oncology, Chicago, IL, University of Illinois at Chicago, Chicago, IL, Boston Medical Center, Boston, MA, Department of Health Studies, Division of Epidemiology, University of Chicago, Chicago, IL, Center for Pharmacoepidemiology and Pharmacoeconomic Research, University of Illinois at Chicago, Chicago, IL Abstract Disclosures Research Funding U.S. National Institutes of Health Background: Adjuvant intravenous bisphosphonates (IV BP) reduce the risk of skeletal-related events (SRE) in patients with multiple myeloma (MM). We examined the effects of bisphosphonate utilization patterns (adherence, cumulative dose and frequency) on risk of SRE. Methods: Patients aged 65 years or older and diagnosed with first primary MM between 2001 and 2011 were identified using the Surveillance, Epidemiology and End Results (SEER)-Medicare linked database. Patients receiving at least one dose of IV BP after MM diagnosis were identified and 5-year SRE-free survival was estimated using the Kaplan-Meier method stratified by demographic groups and compared with the log rank test. Cox proportional hazards models were fit to determine the association between IV BP utilization patterns and SRE after propensity score matching. We investigated the outcome of multiple recurrent SRE using the approach of Andersen-Gill, and estimated subdistribution hazard ratios (SHR) and 95% confidence intervals for risk of first SRE, accounting for death as competing risk. Results: The final cohort included 9176 MM patients with a median age of 76 years. The adjusted 5-year competing-risk SRE model showed a 48% reduction in risk of SRE (95% CI 0.49-0.55) with use of IV BP. In multivariable analyses taking into account competing risks, greater adherence to IV BP, higher cumulative IV BP dose and more frequent administration were all associated with a statistically significant reduction in SRE risks (See Table). Conclusions: Use of IV BP in patients with MM was associated with significant reduction in SRE risk over the 5-year period after MM diagnosis. The effectiveness of IV BP therapy was greater with increasing cumulative dose, adherence to and greater frequency of IV BP administration. Adherence Cumulative dose Frequency of administration Adjusted Relative risk (HR) 95% CI Relative risk (HR) 95% CI Relative risk (HR) 95% CI Untreated (Matched) 1.15 1.03 1.28 Untreated (Matched) 1.32 1.20 1.48 Untreated (Matched) 1.24 1.13 1.36 0.01-0.19 Ref 1-3 Ref < Q12w Ref 0.20-0.39 0.83 0.74 0.93 4-6 0.80 0.71 0.90 Q12w-Q8w 0.83 0.75 0.92 0.40-0.59 0.71 0.63 0.81 7-9 0.73 0.64 0.83 Q8w-Q4w 0.59 0.53 0.64 0.60-0.79 0.57 0.50 0.64 10+ 0.60 0.54 0.67 Q4w and above 0.48 0.42 0.55 0.80-1.00 0.45 0.40 0.51