Primary Amyloidosis Treated with Bortezomib with a Clinical and Radiological Response.

INTRODUCTION: Primary amyloidosis is a plasma cell dyscrasia related to multiple myeloma. The treatment for primary amyloidosis is very similar to the treatment used for multiple myeloma. A new agent, bortezomib, has shown promising results for the treatment of multiple myeloma, but has not yet been used for the treatment of primary amyloidosis. We report a case of a patient with primary amyloidosis who was treated with bortezomib as a 2nd line agent and had significant clinical and radiological regression of disease.

CASE PRESENTATION: A 56 yr old male presented with complaints of anorexia, weight loss, shortness of breath, and parathesias, and RUQ pain. Physical examination and subsequent radiologic studies showed an enlarged liver mass. Laboratory data was significant for elevated alkaline phosphatase and an IgG lambda monoclonal gammapathy in both the urine and serum. A liver biopsy revealed diffuse infiltration of hepatic parenchyma by amyloid deposits. A bone marrow examination revealed 7% plasma cells. His urine immunoelectrophoresis confirmed the presence Bence Jones proteins and a monoclonal IgG lamda spike. Additional work up revealed that he had both renal and cardiac involvement. The patient was treated with alkeran 12 mg days 1–4, thalidomide 200 mg, and dexamethasone 20 mg days 1–4, 9–12, and 17–20, with a good response initially. Seven months into treatment the patient developed a gastrointestinal bleed requiring colonoscopy. Endoscopy and biopsy findings revealed amylodosis involvement of the colon. The patient was re-treated with the same regimen, this time with a partial response, but the medications were discontinued secondary to the worsening of paresthesias and postural hypotension. 2 ½ years after his initial diagnosis, bortezomib was initiated. An excellent clinical and radiological response was seen, with a reduction in the hepatic size from 20 cm to 10 cm, improved cardiac and renal function, and disappearance of the monoclonal protein from his urine.

DISCUSSION: In the past few years the advances in the treatment of primary amyloidosis has suggested that intensive chemotherapy may produce disease remission and dramatic clinical improvement in selected patients. Unfortunately, the rarity and rapid progression of this disease often delays diagnoses until multiorgan involvement limits the ability to treat. Due to the similarities in treatment between amyloidosis and myeloma, data was extrapolated from studies conducted in myeloma, and subsequently applied in this patient. A randomized phase III multicenter trial compared bortezomib with high dose dexamethasone in 669 patients with relapsed/refractory myeloma (APEX™ trial). The overall response rate (38 versus 18 percent) and complete (6 versus 0.6 percent) response rates were significantly higher in patients receiving bortezomib. Patients receiving bortezomib demonstrated a median time to progression of 6.2 months versus 3.5 months for those receiving dexamethasone. Estimated one-year survival was significantly longer for bortezomib-treated patients (80 versus 66 percent). The positive results from this trial, suggested that bortezomib might also have a beneficial role in the treatment of primary amyloidosis. This case shows a documented regression of this patient’s amyloidosis due to bortezomib treatment, further studies of bortezomib in primary amyloidosis need to be performed to validate this possibility.