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Case Study: Immunomodulatory Mechanism and Antimyeloma Effect of Daratumumab

By: Noelle Cutter, PhD
Posted: Tuesday, April 13, 2021

Patients with multiple myeloma and plasma cell leukemia (PCL) transformation tend to have a poor prognosis due to a high level of resistance to conventional therapy. A recent case study, presented by Yu Wu, MD, PhD, and colleagues of the Sichuan University in Chengdu, China, featured a 42-year-old man with resistant multiple myeloma who had PCL transformation and was successfully treated with daratumumab. The patient experienced complete remission followed by autologous hematopoietic stem cell transplantation (auto-HSCT). The details of this case presentation were published in Therapeutic Advances in Hematology.

“To the best of our knowledge, our case is the first report of daratumumab treatment of relapsed/refractory multiple myeloma transformed PCL resulting in complete remission and followed by auto-HSCT,” wrote the authors. “Daratumumab may serve as an ideal bridging salvage chemotherapy for further treatment, such as chimeric antigen receptor T-cell therapy or HSCT.”

The patient had been diagnosed with multiple myeloma and underwent six cycles of bortezomib-based chemotherapy. PCL was diagnosed upon the development of hyperleukocytosis and disseminated intravascular coagulation. Daratumumab therapy was administered, and the patient experienced complete remission after four doses. The patient underwent successful auto-HSCT and remained in complete remission. 

Flow cytometry was conducted during daratumumab treatment to evaluate immune cell dynamics weekly. The authors reported significant downregulation of natural killer (NK) cells, B cells, and CD38-positive regulatory T cells after 4 weeks of treatment. The proportion of T cells increased, with a higher increase in CD8-positive T cells than CD4-positive T cells. NK cells with high CD38 expression showed a more significant decrease than NK cells with low expression of CD38 (13.7% before treatment, 1.2% after treatment, compared with 2.7% and 0.8%, respectively). 

Disclosure: The study authors reported no conflicts of interest.



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