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After evaluating the existing literature and grading recommendations using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) method, experts from the Bone Working Group (BWG) of the International Myeloma Working Group (IMWG) have issued updated clinical practice guidelines for the management of multiple myeloma-related bone disease. These were published in the February 2021 edition of Lancet Oncology.1
The grading approach evaluates recommendations according to the quality of available evidence, separating them into four different categories from A to D. Below, we summarize the highest quality of evidence recommendations (Grade A) provided for newly diagnosed and relapsed/refractory (R/R) multiple myeloma (MM); other recommendation grades, when mentioned, will be noted as such.
You can find a synopsis of the updated treatment recommendations by experts from the working group for myeloma-related bone disease in Table 1 below.
Table 1. Summary of revised Grade A recommendations for the treatment of myeloma-related bone disease*
MM, multiple myeloma; R/R, relapsed or refractory. |
|
Patient population |
Patients with newly diagnosed and R/R myeloma |
---|---|
Choice |
First option |
Zoledronic acid (regardless of the presence of myeloma-related bone disease on imaging) for patients with newly diagnosed or R/R MM; also consider for patients at biochemical relapse |
|
Denosumab (only in the presence of myeloma-related bone disease on imaging; also consider for patients with renal impairment) |
|
Second option |
|
Pamidronic acid (when first-option agents are not available or contraindicated) |
|
Administration |
Zoledronic acid: 4 mg administered intravenously over 15-minute infusion |
Pamidronic acid: 30 mg or 90 mg administered intravenously over 45-minute (for 30 mg) or 2-hour (for 90 mg) infusion |
|
Denosumab: subcutaneous injection of 120 mg |
|
Duration and frequency |
Zoledronic acid |
Monthly during initial therapy and in patients with less than very good partial response (VGPR) |
|
If patients achieve a VGPR or better after receiving monthly administration for at least 12 months, the treating physician can consider decreasing the frequency of dosing to every 3 months or, on the basis of osteoporosis recommendations, to every 6 months or yearly, or discontinuing zoledronic acid |
|
If discontinued, it should be reinitiated at the time of biochemical relapse to reduce the risk of new bone event at clinical relapse |
|
Denosumab |
|
Continuously, monthly until unacceptable toxicity |
|
If discontinued, a single dose of zoledronic acid should be given to prevent rebound effects at least 6 months after the last dose of denosumab; also consider giving denosumab every 6 months |
|
Monitoring and preventive measures |
Creatinine clearance and serum electrolytes (monthly) for zoledronic acid, plus urinary albumin (monthly) for pamidronic acid should be monitored monthly, and dose adjustments should be made accordingly; these tests are not needed for denosumab |
Dental health (at baseline, then at least annually or if symptoms appear) for both bisphosphonates and denosumab |
|
Calcium and vitamin D supplementation is recommended for all patients for both bisphosphonates and denosumab, especially for those with renal impairment, but only after the normalization of serum calcium concentration in case of hypercalcemia |
|
Patient education for early recognition and reporting of adverse events for both bisphosphonates and denosumab |
The BWG of the IMWG recommend balloon kyphoplasty and vertebroplasty (Grade C) for patients with painful vertebral compression fractures. Radiotherapy (Grade C) is suggested for uncontrolled pain, impeding or symptomatic spinal cord compression, or pathological fractures. The algorithmic approach used to guide the decision-making process of treating patients with neurologic signs and symptoms due to spinal cord compression is presented in Figure 1.
Figure 1. Recommendations for the use of cement augmentation, radiotherapy, and surgery in vertebral complications due to MM*
BKP, balloon kyphoplasty; CT, computed tomography; MRI, magnetic resonance imaging; SINS, spinal instability neoplastic score; VAS, visual analogue scale.
*Adapted from Terpos et al.1
Table 2. Considerations for the prevention of skeletal-related events during the COVID-19 pandemic*
MM, multiple myeloma. |
|
Patient population |
Patients with symptomatic MM |
---|---|
Choice |
First option |
Three monthly infusions of zoledronic acid |
|
Second option |
|
At home denosumab administration |
|
Administration |
For responding patients, subcutaneous administration of denosumab may be preferred over the intravenous infusion of bisphosphonates to reduce hospital visits or the length of hospital stay |
These recommendations aim to provide an optimal standard of care for the treatment of myeloma-related bone disease. The choice of bone-targeted agent, or any of the other approaches—cement augmentation, radiotherapy, and surgery—should be carefully considered according to the patients’ needs, presence of pathological fractures, convenience, and cost. Preventative measures are also of crucial importance to avoid treatment-related side effects.
References
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