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 {kappa} 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),1  the {kappa} free light chain (FLC) was increased at 47.2 mg/L (reference interval, 3.3–19.4 mg/L), with a {kappa}/{lambda} FLC ratio of 23 (reference interval, 0.26–1.65). Serum concentrations of β2-microglobulin 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 {gamma} region (32 mg/24 h). In addition, IFE identified a monoclonal {kappa} 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 {kappa} 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 {kappa} 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 µmol/L to 88 µmol/L (reference interval, 62–106 µmol/L). The patient also stated that she felt less fatigued. Her serum {kappa} 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 {kappa} FLC concentration remained increased at 1500 mg/L, however.

  • Why was the patient’s high serum FLC initially not detected by IFE?
  • What are the potential causes of increased FLC after treatment?
  • How can light-chain escape be differentiated from FLC antigen excess?


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