Lack of response to thalidomide in plasmacytomas

Abstract

We read with interest the short report by Bladéet al (2000) regarding the lack of response to thalidomide in five patients with extramedullary plasmacytomas. Two of the patients showed reduction in paraprotein/light-chain excretion but with progressive extraosseous plasmacytomas, whereas the remaining three had progression of their plasmacytomas with no decrease in the paraprotein. From the data, these three appeared to have intraosseous plasmacytomas. Recently, we reported our results in a series of 27 patients (Myers, et al 2000, 2001) treated with thalidomide (plus dexamethasone in eight cases). Of these, three patients had plasmacytomas. The first, aged 68 years, had a soft-tissue plasmacytoma in the chest wall at the time treatment with thalidomide was started. He had a serum paraprotein level of 23 g/l (IgAλ). He showed a rapid, sustained response to thalidomide at a dose of 100 mg/d, to a current level of 3·8 g/l on 50 mg/d thalidomide. However, his chest mass remains unchanged in size. The second patient had an IgAλ paraprotein of 41 g/l, and a second minor band of 6·3 g/l (also IgAκ). His paraprotein bands also responded very quickly to thalidomide 200 mg/d, reducing to 100 mg after 1 month. However, after 2 months' treatment, the patient developed a large intraosseous lesion in his skull that required radiotherapy. The thalidomide was discontinued during this period, but recommenced 1 month later at a dose of 50 mg/d with a continued fall in paraprotein, even at this low level dosage. The current paraprotein levels are 4·3 g/l for the ‘major’ band and 1·1 g/l for the ‘minor’ band. The third patient, aged 51 years at diagnosis, had a non-secretory myeloma with aggressive bony disease. Initially, he was treated with Z-Dex chemotherapy and subsequently received a peripheral stem-cell transplant. He relapsed 1 year after this, but responded to thalidomide (plus melphalan) with a reduction from > 30% marrow plasma-cell infiltrate to < 5%. However, he developed a large soft-tissue mass over his right scapula during this time. Hence, we have seen a similar lack of response to thalidomide in the plasmacytomas but a marked improvement in serum/urinary protein levels, as found in two of the patients described in the series of Bladéet al (2000). It is interesting to speculate why there should be such a significant difference in response when presumably thalidomide can reach these vascular areas easily, and possibly it may imply a difference in the malignant cell itself. Alternatively, it may be related to the differing environments in the extramedullary sites compared with that in the bone marrow stroma, where modulation of adhesion molecules and modulation via cytokines may play a role in the action of thalidomide. The phenomenon described by Bladéet al (2000) appears to be well recognized, although not well reported (Juliusson et al, 2000). A further analysis of cells and environment in plasmacytomas may help to understand both the mechanism(s) of action of thalidomide as well as the nature of the plasmacytoma. In the meantime, therapeutic strategies combining radiotherapy with thalidomide may be necessary when plasmacytomas are part of the clinical problem.