B cells, plasma cells, or both may act as clonogenic cells in multiple myeloma. Circulating CD20-positive B cells bearing identical immunoglobulin H (IgH) rearrangements as autologous plasma cells circulate in most multiple myeloma patients. In
B cells, plasma cells, or both may act as clonogenic cells in multiple myeloma. Circulating CD20-positive B cells bearing identical immunoglobulin H (IgH) rearrangements as autologous plasma cells circulate in most multiple myeloma patients. In addition, plasma cells from some (~ 20%) multiple myeloma patients express CD20. In view of these data, a phase II trial using single-agent rituximab (Rituxan) was initiated in these patients.
The trial was organized according to the Simon two-stage design: 12 patients were treated initially, with an additional 13 patients accrued if less than one response was observed. As part of the study, patients received one cycle of rituximab (375 mg/m² intravenously [IV] weekly × 4) and were reassessed at 12 weeks. Following one cycle of rituximab, patients with stable disease (SD) or a partial response (PR) received a second course of rituximab. Any patients achieving a complete response (CR) were observed and retreated on recurrence. CD20 expression was determined by flow cytometric analysis on bone marrow and peripheral blood B cells, as well as plasma cells before and, when possible, after rituximab therapy.
As of August 1999, 13 multiple myeloma patients have been enrolled. Of these patients, nine have completed therapy, and one did not participate in a planned second cycle of therapy. Median number of prior treatments was three (range, one to six).
Treatment was well tolerated. One patient developed moderate hemoptysis after one cycle of rituximab. A detailed work-up, including bronchoscopy, was unrevealing, and the hemoptysis resolved on its own.
All patients circulating B cells (CD19 positive) were CD20 positive. Of 11 patients, 5 expressed CD20 on their bone marrow plasma cells (CD138 positive, CD38 positive, CD45RA negative). CD20 expression on these patients bone marrow plasma cells was characterized as follows: CD20low (N = 2), heterogeneous with presence of both CD20high and CD20negative plasma cells (N = 2), and CD20high (N = 1).
Of the nine patients who completed therapy, one PR (6 months) occurred in a patient who had mostly (68%) CD20-positive bone marrow plasma cells, and one patient who had CD20-negative bone marrow plasma cells still has SD (11+ months).
CONCLUSIONS: These studies provide the first report of response in a multiple myeloma patient treated with serotherapy directed at CD20. Accruals and evaluations for response are ongoing.
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