Amyloidosis: Detect Early, Treat Broadly

Introduction: AL Amyloidosis is a systemic disorder often caused by deposition of monoclonal protein from underlying plasma cell dyscrasia resulting in nephrotic range proteinuria in addition to causing cardiomyopathy, arrhythmia, hepatosplenomegaly, neuropathy, macroglossia, and autonomic dysfunction. Case Description: A 62-year-old male with hypertension, GERD, asthma, and BPH, is referred to nephrology clinic for progressive renal dysfunction and nephrotic range proteinuria after being evaluated by cardiology for syncope and orthostatic hypotension. Cardiac studies include ECG with low voltage, ECHO with severe left ventricular hypertrophy, event monitor recordings with atrial tachycardia, PAC, and PVC. He had lost 80lbs over months along with loss of appetite, back pain, generalized intermittent sharp nerve pain, lower extremity edema and nosebleeds. Notable labs were proteinuria of 6.1g/day with macroalbuminuria of 3.6g/g, serum creatinine 2.02 mg/dL and eGFR of 34 mL/min/1.73m2. Workup included negative HIV, complements- C3, C4 WNL, ANA w/ reflex <1:80, ANCA serologies, PR3, MPO, PLA2R-ab, anti-GBM. Serum free light chains showed elevated kappa 8.68 mg/dl, lambda 3.99 mg/dl and K/L ratio 2.18. SPEP showed abnormal IFE and Lambda predominance. Given the constellation of symptoms of the patient's clinical presentation, kidney biopsy was pursued that confirmed AL amyloidosis. Flow cytometry revealed abnormal plasma cells without an increase in blasts. He then underwent a bone marrow biopsy that showed findings consistent with plasma cell neoplasm in conjunction with AL amyloidosis. His BNP was 731, Troponin 39. Because of symptomatic cardiac involvement at time of diagnosis, he was not a candidate for autologous HCT and hence was treated with CyBorD and daratumumab. Melphalan was not used due to cardiac involvement. His kidney function continued to decline on therapy due to recurrent AKIs from hypotension as well as his perinephric hematoma after kidney biopsy; he was ultimately started on dialysis 9 months after diagnosis. Discussion: This case highlights that early diagnosis is paramount to safeguarding treatment options., Patients eligible for treatment of AL Amyloidosis and their underlying plasma cell dyscrasia have hematologic response in about 1/2 of cases with improvement of end-organ function. Among patients receiving autologous SCT as first-line therapy, most achieve complete response or very good partial response.