Sharply increased serum free light-chain concentrations after treatment for multiple myeloma.

A 53-year-old woman presented to the orthopedic department with severe diffuse muscular and bone pain. An x-ray of her right upper extremity revealed a lytic destructive lesion in the right humerus. Computed tomography scans showed multiple lytic lesions in the spine and pelvis, and a biopsy confirmed the presence of 70% plasma cells, which were light chain restricted. The patient was referred to a hematologist. Although no monoclonal protein was detected in the serum by protein electrophoresis or by immunofixation electrophoresis (IFE), the free light chain (FLC) was increased at 47.2 mg/L (reference interval, 3.3–19.4 mg/L), with a / FLC ratio of 23 (reference interval, 0.26 –1.65). Serum concentrations of 2microglobulin and albumin were 248 nmol/L (reference interval, 59.5–153 nmol/L) and 37 g/L (reference interval, 34 – 47 g/L), respectively. The urine protein concentration was not increased, but protein electrophoresis revealed a small M (monoclonal) spike in the region (32 mg/24 h). In addition, IFE identified a monoclonal light chain (Bence Jones protein). On the basis of these findings, the patient was informed that she had stage I (International Staging System) oligosecretory/nonsecretory multiple myeloma (MM). The patient underwent surgical repair of her right humerus and was evaluated 1 month after her surgery. At that point, a second serum FLC measurement showed a FLC concentration of 68.2 mg/L. The patient’s hematologist recommended close observation in lieu of initiating therapy because of her lack of symptoms. The patient’s serum FLC concentration was monitored monthly and remained 50 mg/L for the next 3 months. Five months after diagnosis, the patient began to complain of mild fatigue, shortness of breath, and palpitations. A 10-fold increase in the urinary M protein to 333 mg/24 h was noted, along with a decrease in the blood hemoglobin concentration to 79 g/L (reference interval, 120 –155 g/L) and an increase in the calcium concentration to 2.80 mmol/L (reference interval, 2.22–2.52 mmol/L). Her hematologist recommended initiation of treatment, and the patient was enrolled in a clinical trial protocol consisting of lenalidomide (25 mg/day) and dexamethasone (40 mg/ day) administered for 21 days of a 28-day cycle. At 1 month after initiation of treatment, the patient was noted to be tolerating the regimen well, with an increase in her hemoglobin to 91 g/L, a minimal decrease in serum IgG from a pretreatment value of 2.95 g/L to 2.71 g/L (reference interval, 6.00 –15.00 g/L), and a reduction in her serum creatinine concentration from 115 mol/L to 88 mol/L (reference interval, 62–106 mol/L). The patient also stated that she felt less fatigued. Her serum FLC concentration, however, was inexplicably increased to 2180 mg/L (Fig. 1). By her next follow-up appointment a month later, the patient had completed 2 full cycles of the lenalidomide and dexamethasone regimen and showed evidence of continued response, as evidenced by a rise in the hemoglobin concentration to 105 g/L and a decrease in urinary protein excretion to 132 mg/24 h. The patient’s serum FLC concentration remained increased at 1500 mg/L, however.