What is the best course of action for a patient over 60 suspected of having multiple myeloma?

Diagnostic and Treatment Approach for Patient Over 60 with Suspected Multiple Myeloma

For a patient over 60 suspected of having multiple myeloma, immediately obtain serum protein electrophoresis with immunofixation, complete blood count, comprehensive metabolic panel including calcium and creatinine, serum free light chains, 24-hour urine protein electrophoresis, bone marrow biopsy with FISH cytogenetics, and skeletal survey to confirm diagnosis and assess for end-organ damage (CRAB criteria). 1, 2, 3, 4

Initial Diagnostic Workup

Essential Laboratory Tests

• Serum protein electrophoresis (SPEP) with immunofixation to detect and characterize the monoclonal protein 1, 4
• 24-hour urine collection for protein electrophoresis and immunofixation—random urine samples are insufficient and cannot replace this test 1, 4
• Serum free light chain assay with kappa/lambda ratio, particularly critical when standard SPEP is negative 4
• Complete blood count to evaluate for anemia (hemoglobin <10 g/dL or ≥2 g/dL below normal) 1, 3
• Serum calcium and creatinine to assess for hypercalcemia (>11.5 mg/dL) and renal insufficiency (creatinine >2 mg/dL or clearance <40 mL/min) 1, 3
• Serum β2-microglobulin, albumin, and LDH for staging via Revised International Staging System 4, 5

Bone Marrow Assessment

• Unilateral bone marrow aspirate and/or biopsy to quantify plasma cell infiltration (≥10% clonal plasma cells required for diagnosis) 1
• FISH cytogenetics to detect high-risk features including del(17p), t(4;14), t(14;16), which are critical for risk stratification and treatment planning 1, 3, 6
• Standard metaphase cytogenetics should also be performed despite lower yield (20%) as it provides additional prognostic information 1

Imaging Studies

• Full skeletal survey with plain radiographs including spine, pelvis, skull, humeri, and femurs as the standard approach for detecting lytic bone lesions 1, 4
• MRI of spine and pelvis if symptomatic, if solitary plasmacytoma is suspected, or if spinal cord compression is a concern 1, 4

Diagnostic Criteria Confirmation

The diagnosis requires ≥10% clonal bone marrow plasma cells AND evidence of end-organ damage using CRAB criteria: 1, 3, 6

• Calcium: >11.5 mg/dL 1, 3
• Renal insufficiency: Creatinine >2 mg/dL or clearance <40 mL/min 1, 3
• Anemia: Hemoglobin <10 g/dL or ≥2 g/dL below normal 1, 3
• Bone lesions: Lytic lesions, severe osteopenia, or pathologic fractures 1, 3

Critical Distinction: Do NOT Treat Asymptomatic Disease

• If the patient has smoldering (asymptomatic) myeloma (monoclonal protein ≥3 g/dL and/or ≥10% plasma cells BUT no CRAB criteria), immediate treatment is NOT recommended—observation with monitoring at 3-6 month intervals is appropriate 1, 2
• Only initiate treatment when symptomatic myeloma with CRAB criteria is confirmed 1, 2

Treatment Approach for Patients Over 60 (Non-Transplant Eligible)

For elderly patients over 60 who are not transplant candidates, the standard of care is oral melphalan/prednisone combined with a novel agent—either bortezomib (VMP regimen) or thalidomide (MPT regimen). 1, 2

First-Line Treatment Options

Bortezomib/Melphalan/Prednisone (VMP) is a recommended standard regimen: 1, 2

• Bortezomib 1.3 mg/m² subcutaneously on days 1,8,15,22
• Melphalan 9 mg/m² orally days 1-4
• Prednisone 60 mg/m² orally days 1-4
• Repeated every 35 days 2

Alternative: Melphalan/Prednisone/Thalidomide (MPT) is also approved and effective 1

Lenalidomide/Low-Dose Dexamethasone (Rd) is another option: 2

• Lenalidomide 25 mg orally days 1-21
• Dexamethasone 40 mg orally days 1,8,15,22
• Repeated every 28 days 2

Important Caveat for Neuropathy

• Bendamustine plus prednisone is specifically approved for patients who have clinical neuropathy at diagnosis that precludes use of thalidomide or bortezomib 1

Risk Stratification Impact

High-Risk Disease Features

• Presence of del(17p), t(4;14), t(14;16), t(14;20), gain 1q, or p53 mutation constitutes high-risk myeloma 6, 7
• For high-risk patients over 60, a bortezomib-containing regimen is particularly important as it has shown superior outcomes in this population 8, 6

Critical Management Considerations

Hypercalcemia Management

• If hypercalcemia (>11.0 mg/dL) is present, immediately initiate aggressive IV hydration with normal saline at 150-200 mL/hour to achieve urine output >100 mL/hour 2, 4
• Bisphosphonates are the most effective therapy for hypercalcemia in myeloma and should be administered 4

Renal Insufficiency

• In patients with renal insufficiency and high tumor burden, aggressive hydration and rasburicase are recommended to prevent tumor lysis syndrome 2
• Do not delay chemotherapy for extended periods while attempting conservative measures alone, as this worsens outcomes 2
• Bortezomib can be administered without dose adjustment in renal impairment and should be given after dialysis if the patient requires it 9

Supportive Care

• Long-term bisphosphonates should be initiated to reduce skeletal events 2
• Monitor diabetic patients closely as hypoglycemia and hyperglycemia can occur with bortezomib treatment 9

Common Pitfalls to Avoid

• Do not treat smoldering myeloma—this leads to unnecessary toxicity without survival benefit 1, 2
• Do not rely on random urine samples—always obtain 24-hour urine collection for accurate assessment 1, 4
• Do not skip FISH cytogenetics—high-risk features fundamentally change treatment approach and prognosis 1, 6
• Do not use melphalan/prednisone/lenalidomide (MPR) as it was not superior to dual combination therapy and is not approved 1