Best treatment strategies in high-risk multiple myeloma: navigating a gray area

A previously healthy 62-year-old man presented to his primary care physician with a 3-month history of fatigue and unremitting back pain. Physical examination revealed mucosal pallor, point tenderness at T10-T12, and a normal neurologic examination with preserved lower extremity strength and sphincter tone. Laboratory work-up disclosed hemoglobin 10.1 g/dL with mean corpuscular volume of 101 fL and otherwise normal blood cell counts; reticulocytes, 0.98%; stable creatinine, 1.1 mg/dL; calcium, 9.1 mg/dL; albumin, 3.4 g/dL; β2-microglobulin, 5.7 mg/L; lactate dehydrogenase (LDH), 397 IU/L; and normal liver function tests. Bone survey showed lytic lesions at T10, T12, and throughout the axial skeleton and osteopenia. Serum protein electrophoresis (SPEP) demonstrated a 3.5 g/dL monoclonal peak in the gamma region, with monoclonal immunoglobulin G and lambda light chain detected on immunofixation. Serum free light chain (sFLC) ratio was 0.0001. Twenty-four-hour urine protein electrophoresis (UPEP) was normal. Bone marrow biopsy showed 60% infiltration with lambda light chain-restricted plasma cells staining positive for CD138 and CD56 and negative for CD45 by flow cytometry (Fig 1). Congo red stain on bone marrow biopsy and fat pad aspirate was negative for amyloid light-chain deposition. Cytogenetics of the malignant cells identified a t(4;14) translocation, confirming the diagnosis of high-risk, International Staging System stage III immunoglobulin G lambda multiple myeloma (MM). The patient began treatment with lenalidomide, bortezomib, and dexamethasone (RVD) plus monthly intravenous zoledronic acid therapy. He has tolerated therapy well, and the monoclonal protein peak is rapidly declining. He is now referred to discuss indications for autologous stem-cell transplantation (ASCT) and overall prognosis.