When to Start Pulse Steroids in Suspected Multiple Myeloma
Do not wait for bone marrow biopsy confirmation—start pulse steroids immediately when a patient meets CRAB criteria (hypercalcemia, renal insufficiency, anemia, or bone lesions) or has an extremely elevated kappa/lambda ratio (≥100 or ≤0.01) along with ≥10% clonal plasma cells, as these are myeloma-defining events requiring urgent treatment. 1, 2
Diagnostic Criteria That Trigger Immediate Treatment
The 2014 International Myeloma Working Group updated criteria allow treatment initiation based on specific biomarkers without waiting for end-organ damage to worsen 1:
- Abnormal serum free light chain (FLC) ratio ≥100 (involved kappa) or ≤0.01 (involved lambda) is itself a myeloma-defining event when accompanied by ≥10% clonal bone marrow plasma cells 1
- Any CRAB feature present: calcium >11.5 mg/dL, creatinine >2 mg/dL, hemoglobin <10 g/dL, or osteolytic bone lesions 1, 3
- ≥60% clonal plasma cells on bone marrow examination 1
- >1 focal lesion ≥5mm on MRI studies 1
Clinical Algorithm for Treatment Initiation
Immediate Treatment Scenarios (Start Steroids NOW):
Renal failure from myeloma requires the most urgent intervention 1, 2:
- Start bortezomib and dexamethasone-based regimens as soon as possible 1
- High-dose dexamethasone (40mg days 1-4,9-12,17-20) provides rapid tumor reduction 4
- Avoid nephrotoxic drugs and maintain euvolemia 1
- Aggressive hydration with normal saline and bisphosphonates for concurrent hypercalcemia 2
Hypercalcemic crisis (calcium >11.5 mg/dL) 3:
Symptomatic extramedullary disease (e.g., cranial nerve palsies, spinal cord compression) 4:
- Hospitalization for urgent evaluation 4
- High-dose dexamethasone-containing regimen immediately for urgent cytoreduction 4
When Bone Marrow Biopsy Can Be Obtained First:
If the patient has an elevated FLC ratio but no CRAB criteria and is clinically stable, you can proceed with bone marrow biopsy for confirmation before starting treatment 1. However, this represents smoldering myeloma transitioning to active disease, and delays should be minimal 1.
Critical Pitfalls to Avoid
Delaying treatment while awaiting bone marrow confirmation in symptomatic patients increases morbidity and mortality 2. The NCCN explicitly recommends immediate intervention in patients with clear CRAB criteria 2.
Do not confuse smoldering (asymptomatic) myeloma with active (symptomatic) disease 2:
- Smoldering myeloma: M-protein ≥3 g/dL and/or 10-60% clonal plasma cells WITHOUT myeloma-defining events 1
- Active myeloma: ANY myeloma-defining event (CRAB criteria, FLC ratio ≥100 or ≤0.01, ≥60% plasma cells, or >1 focal MRI lesion) 1
The FLC ratio alone is diagnostic when extreme (≥100 or ≤0.01) with adequate clonal plasma cell burden 1. You do not need to wait for bone marrow if the patient has ≥10% plasma cells on initial aspirate and meets this FLC threshold.
Practical Monitoring Considerations
The FLC ratio is particularly valuable for monitoring treatment response, as it reflects therapy results more rapidly than traditional M-protein measurements due to shorter serum half-life 5. After the first cycle of treatment, 90.6% of patients with early objective response showed decreased FLC versus only 51.8% in those with minimal/stable disease 5.
For patients with light chain-only or non-secretory myeloma, FLC measurement is essential since traditional protein electrophoresis may be unrevealing 5, 1.