Plasma Cell CD20 Expression After Autologous Stem Cell Transplantation in Multiple Myeloma: Primary Aberrant Expression or Receptor up-Regulation
Authors: Khaled Yasser , Solh Melhem M. , Ward David , Chang Chung-Che 
Published: October 2019

Abstract
Abstract 4538
CD20 is a trans-membrane protein expressed on mature B cells through all stages of their differentiation. However, its expression is down regulated at the point of differentiation into plasma cells and expressed only in 16–22% of mature plasma cells. CD20 expression on plasma cells has been described with both favorable prognosis in association with translocation t(11;14) and unfavorable prognosis in association with plasma cell leukemia. The incidence of CD20 expression on plasma cells from patients with relapsed/refractory multiple myeloma is not well addressed in literature and CD20 testing is not routinely done in this patient population. Additionally, it is not known if CD20 represents a primary aberrant expression in newly diagnosed cases of multiple myeloma or represents a secondary genetic change at the time of relapse related to hypothesized myeloma stem cells.
In order to study the above questions, we retrospectively reviewed the medical records of 92 patients with symptomatic MM who underwent ASCT between January 2008 and December 2011. As of July 2012, 38 patients have relapsed. Bone marrow biopsy and flow cytometry results were available for 33 patients at time of diagnosis and relapse.CD20 expression was positive on plasma cells by flow cytometry in 11 out of 33 patients (33%) at time of relapse. Interestingly, CD20 expression at diagnosis was negative in 4 out of those 11 patients. This up-regulation of CD 20 expression at time of relapse was associated with clonal evolution in two patients (deletion-17 and complex hypodiploid cytogenetics, respectively). Confirmatory immune-histochemical staining for CD20 was positive only in 2 of those 4 patients.

Rituximab Outcomes:
Three of the 11 patients with relapsed disease after autologous transplant were treated with Rituximab/Bortezomib. Rituximab was given weekly for 4 weeks at dose of 375 mg/m2 and Bortezomib was given at dose of 1.3 mg/m2on day 1, 8 &15 for 2–4 cycles. Time to progression for these three patients was 12, 5 and 3 months. These patients were CD20 positive both at time of diagnosis and relapse. An additional patient with primary refractory myeloma and negative CD20 expression at diagnosis was found to be CD20 positive after 5 unsuccessful lines of therapy suggesting CD20 up regulation. This patient achieved complete remission after treatment with weekly Rituximab/Bortezomib × 4 weeks followed by an autologous stem cell transplantation.

Conclusion:
CD20 expression on plasma cells at time of relapse/progression can occur in one third of patients with multiple myeloma and may provide an additional therapeutic target. The cause of discrepancy between CD20 expression by flow cytometry and immune-histochemical staining is unclear and suggests that the two methods may be complementary for a comprehensive evaluation of CD20 expression in multiple myeloma.CD20 up-regulation in patients with relapsed/refractory myeloma who were previously CD20 negative at diagnosis may represent a secondary genetic event heralding a more aggressive disease. Future prospective studies evaluating CD20 expression on plasma cells at different stages of disease progression may optimize the timing for anti-CD20 therapy while harnessing the concept of myeloma stem cells.

Disclosures:
Khaled: Celgene and Takeda Pharmacutical: Honoraria, Speakers Bureau. Solh:Celgene: Speakers Bureau.