International Myeloma Working Group Recommendations for the Treatment of Multiple Myeloma–Related Bone Disease

Abstract

Bisphosphonates (BPs) should be considered in all patients with MM receiving first-line antimyeloma therapy, regardless of presence of osteolytic bone lesions on conventional radiography. However, it is unknown if BPs offer any advantage in patients with no bone disease assessed by magnetic resonance imaging or positron emission tomography/computed tomography. Intravenous (IV) zoledronic acid (ZOL) or pamidronate (PAM) is recommended for preventing skeletal-related events in patients with MM. ZOL is preferred over oral clodronate in newly diagnosed patients with MM because of its potential antimyeloma effects and survival benefits. BPs should be administered every 3 to 4 weeks IV during initial therapy. ZOL or PAM should be continued in patients with active disease and should be resumed after disease relapse, if discontinued in patients achieving complete or very good partial response. BPs are well tolerated, but preventive strategies must be instituted to avoid renal toxicity or osteonecrosis of the jaw. Kyphoplasty should be considered for symptomatic vertebral compression fractures. Low-dose radiation therapy can be used for palliation of uncontrolled pain, impending pathologic fracture, or spinal cord compression. Orthopedic consultation should be sought for long-bone fractures, spinal cord compression, and vertebral column instability.

Zoledronic acid as compared with observation in multiple myeloma patients at biochemical relapse: results of the randomized AZABACHE Spanish trial

“…4 In addition, some randomized trials have shown clinical benefits for bisphosphonates in these patients when they are administered during cytotoxic therapy. [8][9][10] These results and some preclinical studies argue in favor of an antimyeloma effect for the most potent bisphosphonates.…”

“…3 Intravenous bisphosphonates are indicated in patients with MM, with or without detectable osteolytic bone lesions on conventional radiography, who are receiving antimyeloma therapy as well as in patients with osteoporosis or osteopenia resulting from myeloma. 4 Although the main reason for their indication is that bisphosphonates prevent skeletal-related events, there are also controversial data suggesting that zoledronic acid (ZA) has an anti-myeloma effect. This hypothesized antitumor effect is based on findings in pre-clinical studies, [5][6][7] reproduced in small series of patients, 8 and subanalyses of clinical trials, 9,10 particularly, the large MRC-IX trial 9 conducted in newly diagnosed patients treated with either chemotherapy (CVAB) or thalidomide-based therapy (CTD), who were assigned to receive either ZA or clodronate.…”

European Myeloma Network recommendations on the evaluation and treatment of newly diagnosed patients with multiple myeloma

“…69 At present, intravenous bisphosphonates are recommended for all MM patients requiring therapy, which should be continued with active disease and reassumed after disease relapse (1A). 70 It is important to note that denosumab, a monoclonal antibody to RANK-ligand approved for use in breast and prostate cancer metastatic to bone, is currently being tested in a large randomized trial against ZOL, because the smaller randomized trial in fewer than 200 MM patients of denosumab versus ZOL showed an inferior survival in the subset of MM patients treated with denosumab. 71 The currently available data, therefore, do not yet support the use of denosumab for the treatment of myeloma-related bone disease.…”

Vitamin D Deficiency and its Effects on Patients with Multiple Myeloma

“…They can be stopped after approximately 2 years of use, if there is full response or very good partial response. Re-administration of those drugs is recommended, if there is recurrence [18]. The vit D, calcium, phosphate, magnesium and albumin levels and the renal functions should be evaluated before bisphosphonate use in malignant disorders [19].…”