Background: In our efforts to develop novel effective treatment regimens for multiple myeloma we evaluated the potential benefits of combining the immunomodulatory drug lenalidomide with daratumumab. Daratumumab is a novel human CD38 monoclonal antibody which kills CD38+ multiple myeloma cells via antibody-dependent cell-mediated cytotoxicity, complement-dependent cytotoxicity and apoptosis.

Design And Methods: To explore the effect of lenalidomide combined with daratumumab, we first carried out standard antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity assays in which the CD38+ multiple myeloma cell line UM-9 and primary multiple myeloma cells isolated from patients were used as target cells. We also tested the effect of lenalidomide on daratumumab-dependent cell-mediated-cytotoxicity and complement-dependent cytotoxicity of multiple myeloma cells directly in the bone marrow mononuclear cells of multiple myeloma patients. Finally, we determined the daratumumab-dependent cell-mediated cytotoxicity using peripheral blood mononuclear cells of multiple myeloma patients receiving lenalidomide treatment.

Results: Daratumumab-dependent cell-mediated cytotoxicity of purified primary multiple myeloma cells, as well as of the UM-9 cell line, was significantly augmented by lenalidomide pre-treatment of the effector cells derived from peripheral blood mononuclear cells from healthy individuals. More importantly, we demonstrated a clear synergy between lenalidomide and daratumumab-induced antibody-dependent cell-mediated cytotoxicity directly in the bone marrow mononuclear cells of multiple myeloma patients, indicating that lenalidomide can also potentiate the daratumumab-dependent lysis of myeloma cells by activating the autologous effector cells within the natural environment of malignant cells. Finally, daratumumab-dependent cell-mediated cytotoxicity was significantly up-regulated in peripheral blood mononuclear cells derived from 3 multiple myeloma patients during lenalidomide treatment.

Conclusions: Our results indicate that powerful and complementary effects may be achieved by combining lenalidomide and daratumumab in the clinical management of multiple myeloma.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3031697PMC
http://dx.doi.org/10.3324/haematol.2010.030759DOI Listing

Publication Analysis

Top Keywords

multiple myeloma
44
myeloma cells
24
cell-mediated cytotoxicity
24
mononuclear cells
20
myeloma patients
16
cells
15
myeloma
14
antibody-dependent cell-mediated
12
complement-dependent cytotoxicity
12
cells multiple
12

Similar Publications

Patients participating in clinical trials are highly selected and may not represent the general population. The pivotal study of teclistamab (MajesTEC-1), a B-cell maturation antigen (BCMA)xCD3 bispecific antibody, demonstrated impressive response rates and progression free survival in relapsed/refractory multiple myeloma (RRMM) with acceptable toxicity. We performed a retrospective study of 58 patients treated as standard of care at four US academic centers to determine how these results translated to the real-world.

View Article and Find Full Text PDF

Autograft composition and outcome-towards an optimal graft?

Cytotherapy

December 2024

Department of Medicine, Kuopio University Hospital, Kuopio, Finland. Electronic address:

The amount of CD34 cells has been for decades the most important marker of autologous graft quality, but other graft cells, including various lymphocyte subsets, have gained some interest. This review attempts to summarize what is known about autograft cellular composition regarding post-transplant outcomes. The amount of CD34 cells in the graft is associated with tempo of platelet recovery.

View Article and Find Full Text PDF

Metabolic reprogramming induced by PSMA4 overexpression facilitates bortezomib resistance in multiple myeloma.

Ann Hematol

January 2025

Department of Hematology, Navy Medical Center of PLA, Naval Medical University, No. 338 West Huaihai Road, Changning District, Shanghai, 200052, China.

Multiple myeloma(MM) remains incurable with high relapse and chemoresistance rates. Differentially expressed genes(DEGs) between newly diagnosed myeloma and secondary plasma cell leukemia(sPCL) were subjected to a weighted gene co-expression network analysis(WGCNA). Drug resistant myeloma cell lines were established.

View Article and Find Full Text PDF

Depletion of myeloid-derived suppressor cells sensitizes murine multiple myeloma to PD-1 checkpoint inhibitors.

J Immunother Cancer

January 2025

Center for Translational Research in Hematologic Malignancies, Houston Methodist Neal Cancer Center, Houston Methodist Research Institute, Houston, Texas, USA

Background: Cancer immunotherapy using immune checkpoint blockade (ICB) has revolutionized cancer treatment. However, patients with multiple myeloma (MM) rarely respond to ICB. Accumulating evidence indicates that the complicated tumor microenvironment (TME) significantly impacts the efficacy of ICB therapy.

View Article and Find Full Text PDF

The Burden of Multiple Myeloma in China: Trends from 1990 to 2021 and Forecasts for 2050.

Cancer Lett

January 2025

Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Peking University, Beijing 100044, China; Collaborative Innovation Center of Hematology, Soochow University, Suzhou 215006, China. Electronic address:

This study updates the disease burden of multiple myeloma (MM) in thirty-three provincial administrative units in China from 1990 to 2021 and forecast the disease burden for 2050. Data from the 2021 Global Burden of Disease (GBD) database was used for analysis. In 2021, there were an estimated 17,250 new MM cases and 12,984 deaths in China.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!