What is the recommended treatment for a 55-year-old male patient with suspected multiple myeloma, presenting with hypercalcemia, impaired renal function, anemia, and a history of chronic alcohol use?

Diagnosis and Treatment Approach for This Patient with Suspected Multiple Myeloma

Diagnostic Confirmation

This patient meets CRAB criteria for symptomatic multiple myeloma and requires immediate treatment initiation. 1, 2, 3

CRAB Criteria Met:

• Hypercalcemia: Corrected calcium 3.48 mmol/L (13.9 mg/dL) - significantly exceeds the diagnostic threshold of >11.5 mg/dL (2.9 mmol/L) 1, 3
• Renal insufficiency: Creatinine 1.86 mg/dL with elevated urea 62.5 mg/dL - meets criteria for renal dysfunction 3, 4
• Anemia: Hemoglobin 7.7 g/dL - well below the diagnostic threshold of <10 g/dL 3, 5
• Bone lesions: "Moth-eaten" lytic lesions in ribs, diffuse osteopenia with thin cortex on spine imaging 3, 5

Additional Diagnostic Evidence:

• Elevated ESR (64 mm/hr) and elevated LDH (253 U/L) support active disease 5
• Pleural effusion with lymphocyte predominance (55%) consistent with myeloma involvement 6
• Retroperitoneal mass with vascular encasement and hydronephrosis indicates extramedullary disease 7
• Elevated uric acid (12.9 mg/dL) suggests high tumor burden 8

Critical pitfall: The prolonged PT >120 seconds is concerning and requires immediate correction before initiating therapy to prevent bleeding complications. 6

Treatment Strategy

Transplant Eligibility Assessment

This 55-year-old patient is NOT an ideal candidate for immediate autologous stem cell transplantation (ASCT) due to:

• Sub-critical admission status with multiple organ complications 6
• Severe renal impairment (creatinine 1.86 mg/dL) 6, 4
• Significant hypercalcemia requiring urgent management 2, 3
• Chronic alcohol use for 20 years affecting overall fitness 6
• Extramedullary disease with retroperitoneal mass 7

However, age alone does not exclude future transplant consideration after disease control and clinical improvement. 6

Recommended Initial Treatment Regimen

Bortezomib-based triplet therapy is the preferred initial treatment for this patient. 6, 2

Specifically recommend: Bortezomib/Cyclophosphamide/Dexamethasone (VCD) because:

• Bortezomib can be safely administered without dose adjustment in renal impairment 6, 3
• Avoids lenalidomide which requires dose reduction in renal dysfunction 6, 4
• Cyclophosphamide is effective and does not compromise future stem cell collection 6
• Provides rapid disease control for hypercalcemia and renal protection 2, 3

Alternative if VCD unavailable: Bortezomib/Dexamethasone (doublet) 6

• Acceptable for elderly or frail patients, though triplets are preferred 6
• This patient's sub-critical status may warrant starting with doublet then escalating 6

Do NOT use:

• Melphalan-containing regimens (MPT, VMP) initially - these are stem cell toxic and this patient may become transplant-eligible after improvement 6
• Lenalidomide/dexamethasone as monotherapy - requires dose adjustment for renal impairment 6, 4
• VAD regimen (vincristine/adriamycin/dexamethasone) - inferior to modern combinations [2, @15@]

Treatment Administration Details

Bortezomib administration: 6

• Subcutaneous route preferred (reduces neuropathy risk) 6
• Standard dosing can be used without renal adjustment 6, 3
• Herpes zoster prophylaxis with acyclovir is mandatory 6

Dexamethasone dosing: 6

• Use low-dose dexamethasone (40 mg weekly or 20 mg weekly if >75 years) 6
• On bortezomib infusion days, give as pre-medication 9

Treatment duration: 6

• Administer 3-4 cycles initially 6, 2
• Reassess response after 2 cycles 6
• Continue until maximum response or 8-12 cycles if not transplant-eligible 6, 4

Urgent Supportive Care Measures (Must Be Initiated Immediately)

1. Hypercalcemia Management (PRIORITY)

Corrected calcium 3.48 mmol/L (13.9 mg/dL) is life-threatening and requires aggressive treatment: 2, 3

• Aggressive IV hydration with normal saline - 200-300 mL/hour initially (monitor for fluid overload given renal impairment and pleural effusions) 2, 3, 5
• IV bisphosphonates: Zoledronic acid 4 mg IV over 15 minutes OR pamidronate 90 mg IV over 2-4 hours 2, 3, 5
• Calcitonin 4-8 IU/kg SC/IM every 12 hours for rapid effect (works within hours while awaiting bisphosphonate effect) 5
• Furosemide only after adequate hydration to enhance calcium excretion 5
• Avoid thiazide diuretics - these increase calcium reabsorption 5

2. Renal Protection

• Continue aggressive hydration (as above) 2, 3
• Avoid nephrotoxic agents including NSAIDs 5
• Monitor urine output and consider nephrology consultation 4
• The right-sided hydronephrosis from retroperitoneal mass may require urologic intervention (stent or nephrostomy) 7

3. Bone Disease Management

• Long-term bisphosphonates (zoledronic acid 4 mg IV monthly or pamidronate 90 mg IV monthly) to reduce skeletal-related events 2, 3
• Continue indefinitely while on active treatment 2, 3
• Monitor renal function and adjust dosing accordingly 3
• Dental evaluation before starting bisphosphonates to prevent osteonecrosis of jaw 3

4. Anemia Management

• Transfuse packed RBCs to maintain Hb >8 g/dL for symptomatic relief 8, 5
• Erythropoiesis-stimulating agents can be considered after chemotherapy initiation 8

5. Infection Prophylaxis

This patient is at high risk for infections due to: 6, 5

• Immunosuppression from myeloma 5
• Chronic alcohol use 5
• Upcoming chemotherapy 6

Required prophylaxis:

• Acyclovir 400 mg PO twice daily (or valacyclovir 500 mg daily) for herpes zoster prevention with bortezomib 6
• Pneumococcal vaccination (PCV13 followed by PPSV23) 5
• Influenza vaccination annually 5
• Haemophilus influenzae B vaccination 5
• Consider prophylactic antibiotics (fluoroquinolone) given history of recent infection and immunocompromised state 5

6. Thrombosis Prophylaxis

• Full-dose aspirin (81-325 mg daily) is NOT recommended initially due to prolonged PT >120 seconds 6
• Correct coagulopathy first with vitamin K and fresh frozen plasma if needed 6
• Once PT normalized, initiate aspirin prophylaxis 6

7. Pain Management

• Opioid analgesics for bone pain (avoid NSAIDs due to renal impairment) 5
• Consider palliative radiation to symptomatic rib lesions 5, 7
• Vertebroplasty or kyphoplasty if vertebral compression fractures develop 5

Monitoring During Initial Treatment

Assess response after 2 cycles: 6

• Repeat serum protein electrophoresis, immunofixation, and free light chains 4, 5
• Repeat skeletal survey or PET/CT 6
• Bone marrow biopsy if complete response suspected 4
• Monitor calcium, creatinine, and hemoglobin weekly initially 3, 5

If inadequate response after 2-4 cycles:

• Consider switching to alternative regimen (e.g., add lenalidomide if renal function improved) 6, 4
• Reassess transplant eligibility if clinical improvement achieved 6, 4

Special Considerations for This Patient

Chronic Alcohol Use

• Increases risk of hepatotoxicity with chemotherapy 10
• Monitor liver function tests closely 10
• Nutritional support and thiamine supplementation 10
• Consider addiction medicine consultation 10

Extramedullary Disease

• The retroperitoneal mass with vascular encasement is concerning for aggressive disease 7
• May require radiation therapy if causing symptoms or progressing 7
• Consider urology consultation for hydronephrosis management 7
• Extramedullary disease portends poorer prognosis and may require more aggressive therapy 7

Pleural Effusion

• Lymphocyte-predominant effusion (55%) suggests myelomatous involvement 6
• May require therapeutic thoracentesis if symptomatic 6
• Monitor with serial chest X-rays 6

Risk Stratification

This patient requires cytogenetic testing (FISH) to assess risk: 4

• High-risk features: del(17p), t(4;14), t(14;16), t(14;20), gain 1q, p53 mutation 4
• If high-risk cytogenetics present, consider Daratumumab/Bortezomib/Cyclophosphamide/Dexamethasone once stabilized 4
• High-risk patients require more intensive maintenance therapy 4

Future Transplant Consideration

If patient achieves good response and clinical improvement: 6, 4

• Collect stem cells after 3-4 cycles of induction 6
• Proceed to ASCT with melphalan 200 mg/m² conditioning 6, 2
• Lenalidomide maintenance post-transplant for standard-risk disease 4
• Bortezomib plus lenalidomide maintenance for high-risk disease 4

Critical pitfall to avoid: Do NOT delay treatment to determine transplant eligibility - this patient requires immediate therapy due to CRAB criteria. 2, 3