What is the management approach for Multiple Myeloma patients meeting CRAB (Calcium elevation, Renal impairment, Anemia, Bone lesions) criteria?

Management of Multiple Myeloma Patients Meeting CRAB Criteria

Treatment should be initiated immediately in all patients with active multiple myeloma fulfilling the CRAB criteria (hypercalcemia, renal insufficiency, anemia, bone lesions) as these represent end-organ damage requiring prompt intervention. 1

Diagnostic Confirmation

Before initiating treatment, confirm the diagnosis with:

• ≥10% clonal plasma cells on bone marrow examination or a biopsy-proven plasmacytoma 1
• Evidence of end-organ damage (CRAB criteria):
  • Hypercalcemia: serum calcium >11.5 mg/dL 2
  • Renal insufficiency: serum creatinine >2.0 mg/dL or estimated creatinine clearance <40 mL/min 1
  • Anemia: hemoglobin <10 g/dL or ≥2 g/dL below the lower limit of normal 1
  • Bone lesions: lytic lesions, severe osteopenia, or pathologic fractures 1

Treatment Algorithm Based on Age and Transplant Eligibility

For Younger Patients (<65 years or fit patients eligible for transplant)

1. Induction therapy with one of the following regimens:

   • Bortezomib, lenalidomide, dexamethasone (VRd) for 3-4 cycles 3, 4
   • For high-risk patients: Consider daratumumab, bortezomib, lenalidomide, dexamethasone (Dara-VRd) 4

2. Autologous stem cell transplantation (ASCT) following induction 3, 4

3. Maintenance therapy:

   • Standard-risk patients: Lenalidomide maintenance 4, 5
   • High-risk patients: Bortezomib plus lenalidomide maintenance 4, 5

For Elderly Patients (≥65 years or not eligible for transplant)

1. Treatment options include:
   • Bortezomib, melphalan, prednisone (VMP) for approximately 8-12 cycles 1
   • Melphalan, prednisone, thalidomide (MPT) 1
   • Bortezomib, lenalidomide, dexamethasone (VRd) for 8-12 cycles followed by maintenance 3, 4
   • Daratumumab, lenalidomide, dexamethasone (DRd) until progression 3, 4
   • For patients with neuropathy at diagnosis: Bendamustine plus prednisone 1

Special Considerations

Renal Impairment

• Bortezomib-based regimens are preferred as they can be safely administered without dose adjustment 1
• Avoid NSAIDs and maintain adequate hydration 1
• Consider plasmapheresis for severe renal failure with high light chain burden 1

Hypercalcemia

• Aggressive hydration with normal saline 2
• Bisphosphonates (zoledronic acid or pamidronate) 1
• Calcitonin for severe cases 2

Bone Disease

• Bisphosphonates (zoledronic acid or pamidronate) to reduce skeletal-related events 1
• Radiation therapy for painful lesions or impending fractures 1
• Surgical intervention for pathologic fractures or spinal cord compression 1

Anemia

• Erythropoiesis-stimulating agents if symptomatic 1
• Red blood cell transfusions for severe symptomatic anemia 1

Risk Stratification Impact on Treatment

• High-risk features include: del(17p), t(4;14), t(14;16), t(14;20), gain 1q, or p53 mutation 3, 4
• Double-hit myeloma: presence of any two high-risk factors 4
• Triple-hit myeloma: three or more high-risk factors 4
• High-risk patients benefit from more intensive therapy and prolonged maintenance 4, 5

Common Pitfalls to Avoid

• Delaying treatment in patients with clear CRAB criteria - these patients require immediate intervention 1
• Confusing smoldering multiple myeloma (which doesn't require immediate treatment) with symptomatic multiple myeloma 1
• Failing to perform cytogenetic/FISH studies which are essential for risk stratification 1, 4
• Inadequate management of complications like hypercalcemia and renal failure which can lead to increased morbidity and mortality 2, 6
• Using single-agent therapy instead of combination regimens, which have demonstrated superior outcomes 3, 4