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.