Use of bone‐modifying agents and clinical outcomes in older adults with multiple myeloma

Abstract

Background Guidelines recommend bone‐modifying agents (BMAs) for all patients initiating treatment for myeloma. We examined adherence to this recommendation, and BMA effectiveness in the era of bortezomib/lenalidomide‐based therapy among Medicare beneficiaries. Methods From the linked Surveillance, Epidemiology, and End Results‐Medicare registry, we selected beneficiaries receiving anti‐myeloma chemotherapy in 2007‐2013. We matched BMA recipients (within 90 days of first chemotherapy) to nonrecipients using a propensity score, balancing patient‐, disease‐, and therapy‐related confounders. Cumulative incidence of skeletal‐related events (SREs) and overall survival (OS) was compared in proportional hazard models accounting for competing risks and immortal‐time bias. Results Among 4611 patients with median age of 76 years, 51% received BMA. Bone‐modifying agents use remained steady over time (P = .87) and was significantly less frequent for patients who were older, with comorbidities, without prior SRE, and those treated without bortezomib or lenalidomide. In a propensity score‐matched cohort, BMA recipients experienced a lower incidence of SRE (11.0% vs 14.6% at 3 years; subhazard ratio, 0.73; 95% CI, 0.60‐0.89) and better OS (53.3% vs 47.8% at 3 years; hazard ratio, 0.86; 95% CI, 0.77‐0.95). The results were consistent in the subgroup (76%) treated with bortezomib and/or immunomodulatory drugs (IMiDs). The incidence of osteonecrosis of the jaw (ONJ) was 3.2% at 3 years. Conclusions In this observational study, the observed benefits of early BMA administration among patients treated with contemporary anti‐myeloma regimens were similar to historical clinical trials. Frequent omission of BMA highlights a remediable deficiency in the quality of supportive care, and suggests that timely administration may be a useful indicator of quality care in myeloma.

Outcomes of lenalidomide‐ or bortezomib‐based regimens in older patients with plasma cell myeloma

“…We have shown that our claims-based indicators of myeloma severity can provide risk stratification similar to R-ISS and that they predict treatment selection. Prior observations indicate that socio-economic factors (like type of prescription coverage) and supportive care components show a significant association with treatment selection and survival among older patients with myeloma 18,19,34,35. We could not discern the effect of varying drug doses, schedules, impact of interruptions or early discontinuations.…”

“…We classified first-line regimens based on drugs administered within 30 days from the first recorded anti-myeloma therapy, distinguishing lenalidomide, bortezomib, cyclophosphamide, and other common cytotoxic drugs (Table S1). 18,19 Dexamethasone prescriptions were identified among 86% of beneficiaries receiving lenalidomide or bortezomib, and unbilled use of corticosteroids was assumed for others.…”

Multiple-Drugs-Related Osteonecrosis of the Jaw in a Patient Affected by Multiple Myeloma: A Case Report

“…Medication-related osteonecrosis of the jaws (MRONJ) is a drug-related, adverse event characterized by progressive destruction and necrosis of the mandibular and/or maxillary bone in patients treated with drugs identified to be at an increased risk of MRONJ that has been ascertained without prior radiation treatment [ 1 ]. Antiresorptive (e.g., bisphosphonates, denosumab) and antiangiogenic drugs (e.g., anti-VEGF, TKIs, mTOR inhibitors) are the medications most commonly implicated in the development of MRONJ because of the impairment of the bone metabolism they cause [ 2 ]. Such an adverse event, initially described as bisphosphonate-related osteonecrosis of the jaw (BRONJ), was later referred to as drug-related osteonecrosis of the jaw (DRONJ), thus encompassing all osteonecrotic processes associated with drug use regardless of their mechanism of action [ 3 ], as evidence is accumulating for other drugs as well.…”