A 72-year-old Japanese male was diagnosed as having
monoclonal gammopathy of undetermined significance and was followed up without
therapy. Three years later, the patient progressed to symptomatic
multiple myeloma.
Melphalan +
prednisolone was administered as first-line
chemotherapy for ~6 years. Since the patient was judged to exhibit refractory
multiple myeloma, he subsequently received
radiation therapy on the lumbar spine. The patient was enrolled in a clinical trial and received
lenalidomide + lowdose
dexamethasone (Rd)
therapy. The patient achieved very good partial remission following four cycles of Rd. At this time, large granular lymphocytes (LGLs) increased to 25-40% of peripheral blood leukocytes, however, the LGLs were present in the blood (~8%) prior to
lenalidomide treatment. By flow cytometry of
surface antigens, it was revealed that the LGLs were positive for cluster of differnetiation (CD)2, 7, 8, 16, 56, and 57, and
human leukocyte antigen-D related, however, were negative for CD3, 4 and 5, suggesting that these LGLs predominantly exhibited an natural killer (NK) cell phenotype.
T-cell receptor β gene rearrangement was not detected by polymerase chain reaction. A 51Cr release assay was performed to investigate whether the NK cells actually possessed activity. A low level of M
protein was sustained for ~15 months. This implied the enhancement of immune activation during
lenalidomide treatment. The present case study suggested that LGL cells induced by
lenalidomide may contribute to long-term restraint of myeloma cells. This immune system component may contribute to disease control.