What is the management of CRAB (Hypercalcemia, Renal failure, Anemia, Bone lesions) symptoms in multiple myeloma?

Management of CRAB Symptoms in Multiple Myeloma

The management of CRAB symptoms (Hypercalcemia, Renal failure, Anemia, Bone lesions) in multiple myeloma requires immediate intervention with specific targeted therapies for each manifestation while simultaneously initiating anti-myeloma treatment. 1

Hypercalcemia Management

• Aggressive hydration with normal saline (2-3 L/day) should be initiated immediately to increase calcium excretion and improve renal function 1, 2
• Bisphosphonates, particularly zoledronic acid (4 mg IV) or pamidronate, are the cornerstone of hypercalcemia treatment in multiple myeloma 1, 3
• Zoledronic acid works by inhibiting osteoclastic activity and inducing osteoclast apoptosis, thereby reducing bone resorption and calcium release 3
• For severe hypercalcemia (>14 mg/dL), consider adding calcitonin for rapid but short-term calcium reduction 2
• Avoid thiazide diuretics which can worsen hypercalcemia; loop diuretics may be used after adequate hydration 4

Renal Failure Management

• Immediate hydration with normal saline and urine alkalinization are essential first steps in managing myeloma-related renal impairment 4
• Discontinue all nephrotoxic medications, particularly NSAIDs, which can worsen renal damage 1
• Bortezomib-based regimens are preferred for patients with renal impairment as they can be administered without dose adjustment 1
• Consider therapeutic plasma exchange (TPE) in selected cases with high free light chain levels, although its role remains controversial 4
• Monitor renal function using CKD-EPI formula with cystatin C for more accurate assessment of glomerular filtration rate 4

Anemia Management

• Erythropoiesis-stimulating agents can be considered for symptomatic anemia (hemoglobin <10 g/dL) 5
• Red blood cell transfusions may be necessary for severe symptomatic anemia or when rapid correction is needed 5
• Treat underlying causes such as iron, B12, or folate deficiency if present 5
• The definitive treatment for myeloma-related anemia is effective anti-myeloma therapy 4

Bone Disease Management

• Bisphosphonates (zoledronic acid 4 mg IV monthly) are indicated for all patients with multiple myeloma and bone disease 4, 3
• Whole-body low-dose CT (WBLD-CT) is the preferred imaging modality for detecting and monitoring bone lesions 4
• For vertebral compression fractures, consider balloon kyphoplasty or vertebroplasty to stabilize the spine and reduce pain 4
• Radiation therapy is effective for localized painful bone lesions or at risk of pathological fracture 4
• Surgical intervention may be necessary for impending or actual pathological fractures, particularly in weight-bearing bones 4

Anti-Myeloma Therapy

• Initiate appropriate anti-myeloma therapy immediately, as treating the underlying disease is essential for resolving CRAB symptoms 4, 6
• For transplant-eligible patients, bortezomib, lenalidomide, dexamethasone (VRd) is the standard induction regimen 6, 7
• For high-risk patients, consider daratumumab, bortezomib, lenalidomide, dexamethasone (Dara-VRd) 6, 7
• For transplant-ineligible patients, options include VRd for 8-12 cycles or daratumumab, lenalidomide, dexamethasone (DRd) until progression 6, 7
• For elderly patients (≥65 years), bortezomib, melphalan, prednisone (VMP) for 8-12 cycles is an alternative option 1

Monitoring and Follow-up

• Regular monitoring of serum calcium, renal function, complete blood count, and bone disease is essential 5
• Repeat imaging with WBLD-CT or MRI to assess response of bone lesions to therapy 4
• Monitor for complications of therapy, including thromboembolic events, peripheral neuropathy, and infections 4
• Assess response to therapy using serum and urine protein electrophoresis, serum free light chain assays, and bone marrow examination when appropriate 5

Special Considerations

• Patients with renal failure at presentation should be treated as a medical emergency 4
• For patients with bone disease, oral calcium (500 mg) and vitamin D (400 IU) supplementation is recommended when on bisphosphonate therapy 3
• Avoid unnecessary bone marrow biopsies and imaging in patients with established diagnosis 5
• Consider the risk of osteonecrosis of the jaw with bisphosphonate therapy; dental examination prior to treatment is recommended 3