When should we initiate therapy for multiple myeloma in a patient with hemoglobin 10 g/dL, serum free light chain 1097 mg/L, and light‑chain amyloid cardiomyopathy with preserved left ventricular ejection fraction and pro‑BNP ≈ 7000 pg/mL?

Immediate Treatment Initiation for Light-Chain Amyloid Cardiomyopathy

This patient requires immediate chemotherapy initiation without delay—the presence of cardiac amyloidosis with heart failure (pro-BNP 7000 pg/mL) constitutes an absolute indication for urgent treatment regardless of other myeloma parameters. 1, 2

Why Treatment Cannot Be Delayed

• Cardiac amyloidosis with heart failure is a life-threatening emergency requiring rapid elimination of the amyloidogenic light chain-producing plasma cell clone to prevent progressive cardiac dysfunction and death. 3, 1
• The median survival for patients with NT-proBNP >5,000 pg/mL is only 5.8 months without treatment, placing this patient in the highest-risk category (Stage IV cardiac amyloidosis). 1, 2
• The hemoglobin of 10 g/dL meets CRAB criteria for symptomatic myeloma (anemia threshold), which independently mandates treatment initiation. 4, 5
• The markedly elevated free light chain (1097 mg/L) indicates high disease burden and ongoing production of cardiotoxic light chains that cause direct myocardial damage beyond mechanical amyloid deposition. 3, 6

Optimal Treatment Regimen Selection

Start bortezomib-based chemotherapy immediately—specifically cyclophosphamide-bortezomib-dexamethasone (CyBorD) or daratumumab-bortezomib-dexamethasone (DVd). 5, 7

Why Bortezomib-Based Therapy is Mandatory

• Bortezomib achieves the fastest reduction in amyloidogenic light chains, which is critical when cardiac function is already compromised with preserved LVEF but severely elevated pro-BNP. 4, 5
• Bortezomib can be administered safely without dose adjustment in renal impairment, which is crucial since cardiac amyloidosis patients often have concurrent renal involvement. 5
• Subcutaneous bortezomib once weekly minimizes neuropathy risk while maintaining efficacy—start with twice-weekly dosing for 1-2 cycles if urgent light chain reduction is needed, then transition to weekly. 4, 5

Daratumumab Addition for Cardiac Amyloidosis

• Daratumumab-containing regimens (DRd or DVd) produce rapid complete hematologic responses in AL cardiac amyloidosis with documented improvements in cardiac biomarkers (BNP, troponin) and cardiac function within 3-12 months. 7
• Daratumumab prevents additional amyloid deposition and suppresses direct cardiotoxic effects of circulating light chains beyond simply reducing plasma cell burden. 7, 3

Critical Treatment Contraindications to Avoid

This patient is NOT a candidate for autologous stem cell transplant due to the following absolute contraindications: 1, 2

• Pro-BNP >5,000 pg/mL (patient has 7,000 pg/mL)
• Heart failure with preserved LVEF indicates advanced cardiac amyloid burden
• Transplant-related mortality would be prohibitively high (>50%) in this cardiac risk category

Do not use melphalan-based regimens (melphalan-dexamethasone, VMP) as initial therapy—these are too slow-acting for a patient with advanced cardiac involvement requiring urgent light chain reduction. 5, 1

Mandatory Supportive Care Measures

• Initiate herpes zoster prophylaxis immediately (acyclovir or valacyclovir) for all patients receiving bortezomib-based regimens. 5
• Avoid aggressive diuresis in cardiac amyloidosis—these patients are preload-dependent and excessive diuresis can precipitate cardiovascular collapse despite elevated BNP. 3
• Hold ACE inhibitors and beta-blockers as they are poorly tolerated in restrictive cardiomyopathy from amyloidosis and can cause symptomatic hypotension. 3, 1
• Thromboprophylaxis with aspirin or low-molecular-weight heparin should be started given the combination of myeloma therapy and potential immobility from heart failure. 5

Monitoring Treatment Response

• Measure serum free light chains every 2-4 weeks to assess hematologic response—the goal is complete hematologic response (normal FLC ratio and involved FLC <10 mg/L). 3, 1
• Serial cardiac biomarkers (NT-proBNP, troponin) every 1-3 months track cardiac response, which typically lags 3-6 months behind hematologic response. 7, 3
• Cardiac response requires ≥30% reduction in NT-proBNP (if baseline >650 pg/mL) plus improvement in NYHA class or other cardiac parameters. 3, 1

Common Pitfall to Avoid

Do not delay treatment to "watch and wait" or perform additional staging—every week of delay allows continued light chain deposition and irreversible cardiac damage in a patient already at the highest mortality risk. 3, 1, 2