Abstract
BackgroundGuidelines 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.MethodsFrom 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.ResultsAmong 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.ConclusionsIn 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.
Highlights
Bone‐modifying agents (BMAs), which include intravenous bisphosphonates and denosumab, are integral components of care for patients with plasma cell myeloma
Our objective was to describe practice patterns with regard to the use of bone‐modifying agent (BMA) in the United States (US), factors associated with omission of BMA, and to compare the risk of skeletal‐related events (SREs) and survival according to receipt of BMA as part of initial anti‐myeloma therapy
We examined the association between BMA administration and overall survival (OS) in an extended model which assigns time‐at‐risk for every patient before receipt of BMA to the “untreated” group
Summary
Bone‐modifying agents (BMAs), which include intravenous bisphosphonates (zoledronate and pamidronate) and denosumab (a monoclonal antibody neutralizing the receptor activator of nuclear factor kappa‐Β ligand), are integral components of care for patients with plasma cell myeloma. Addition of BMA to chemotherapy lowers the risk of myeloma‐related skeletal events and improves the quality of life, even in the absence of radiographically overt bone lesions.[1,2,3,4,5,6,7] in the phase 3 Medical Research Council (MRC) Myeloma IX trial, administration of zoledronate (rather than oral clodronate) with anti‐myeloma therapy improved the overall survival (OS, with a hazard ratio [HR] of 0.86) and progression‐free survival (PFS, with HR of 0.89), suggesting a disease‐modifying effect.[5,8] Proposed mechanisms for this effect may involve BMA action on the bone microenvironment and/or direct cytotoxicity to malignant plasma cells.[9,10] As a result, multiple guidelines recommend administration of BMA to all patients initiating anti‐myeloma therapy who do not have prohibitive contraindications (eg, renal failure for bisphosphonates), but adherence to these recommendations in clinical practice is uncertain.[11,12,13] It is uncertain if survival benefit of BMA persists in the era of widespread use of bortezomib and lenalidomide as first‐line therapy, because the MRC Myeloma IX trial did not include these novel, highly active agents. 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
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