Monoclonal antibody-based therapy as a new treatment strategy in multiple myeloma

Donk, Niels W.C.J. van de; S, Kamps; Mutis, Tuna; Lokhorst, Henk M.

doi:10.1038/leu.2011.214

Cited by 73 publications

(49 citation statements)

References 132 publications

(153 reference statements)

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“…The potential benefit of targeting multiple myeloma tumor cells by specific mAbs alone or in combination with other antimultiple myeloma agents has also been demonstrated by other recent experimental and clinical studies (4,(20)(21)(22)(23)(24)(25)(26). For instance, bortezomib was described to synergistically enhance the lysis of ADCC mediated by the CS1 mAb elotuzumab in vitro (27).…”

Section: Discussionmentioning

confidence: 85%

“…On the other hand, the success of anti-CD20 mAbs in the treatment of non-Hodgkin lymphomas and chronic lymphocytic leukemia, illustrated that antibody-mediated immunotherapy can also represent a powerful therapeutic option for hematologic malignancies and stimulated the investigation of antibody therapies for multiple myeloma (4). Daratumumab is a human IgG1 kappa monoclonal antibody that targets CD38, a type II transmembrane glycoprotein, which is highly and uniformly expressed in multiple myeloma (5).…”

Section: Introductionmentioning

confidence: 99%

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Preclinical Evidence for the Therapeutic Potential of CD38-Targeted Immuno-Chemotherapy in Multiple Myeloma Patients Refractory to Lenalidomide and Bortezomib

Nijhof

Groen

Noort

et al. 2015

Clinical Cancer Research

136

115

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Purpose: Novel therapeutic agents have significantly improved the survival of patients with multiple myeloma. Nonetheless, the prognosis of patients with multiple myeloma who become refractory to the novel agents lenalidomide and bortezomib is very poor, indicating the urgent need for new therapeutic options for these patients. The human CD38 monoclonal antibody daratumumab is being evaluated as a novel therapy for multiple myeloma. Prompted with the encouraging results of ongoing clinical phase I/II trials, we now addressed the potential value of daratumumab alone or in combination with lenalidomide or bortezomib for the treatment of lenalidomide-and bortezomib-refractory patients.Experimental Design: In ex vivo assays, mainly evaluating antibody-dependent cell-mediated cytotoxicity, and in an in vivo xenograft mouse model, we evaluated daratumumab alone or in combination with lenalidomide or bortezomib as a potential therapy for lenalidomide-and bortezomib-refractory multiple myeloma patients.Results: Daratumumab induced significant lysis of lenalidomide/bortezomib-resistant multiple myeloma cell lines and of primary multiple myeloma cells in the bone marrow mononuclear cells derived from lenalidomide-and/or bortezomib-refractory patients. In these assays, lenalidomide but not bortezomib, synergistically enhanced daratumumabmediated multiple myeloma lysis through activation of natural killer cells. Finally, in an in vivo xenograft model, only the combination of daratumumab with lenalidomide effectively reduced the tumorigenic growth of primary multiple myeloma cells from a lenalidomide-and bortezomib-refractory patient.Conclusions: Our results provide the first preclinical evidence for the benefit of daratumumab plus lenalidomide combination for lenalidomide-and bortezomib-refractory patients.

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Section: Discussionmentioning

confidence: 85%

Section: Introductionmentioning

confidence: 99%

Preclinical Evidence for the Therapeutic Potential of CD38-Targeted Immuno-Chemotherapy in Multiple Myeloma Patients Refractory to Lenalidomide and Bortezomib

Nijhof

Groen

Noort

et al. 2015

Clinical Cancer Research

136

115

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“…34 For MM patient therapy, the current focus is on combination therapy of mAb with immunomodulatory drugs (IMiDs). 37,38 IMiDs currently used, e.g., lenalidomide and pomalidomide, are described to enhance NK-cell mediated ADCC. 39 Combining DARA with lenalidomide enhanced ADCC-mediated elimination of MM cells.…”

Section: Discussionmentioning

confidence: 99%

Antibody-mediated phagocytosis contributes to the anti-tumor activity of the therapeutic antibody daratumumab in lymphoma and multiple myeloma

Overdijk

Verploegen²,

Bögels³

et al. 2015

mAbs

435

276

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“…148,149 Bisphosphonates are often used for the management of MM patients with bone lesions. The most significant data that indicates that bisphosphonates have an effect on survival of patients with MM came from a recent randomized study of the Medical Research Council IX.…”

Section: Clinical Applications and Therapeutic Targetingmentioning

confidence: 99%

Myeloma as a model for the process of metastasis: implications for therapy

Ghobrial

2012

Blood

173

172

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Multiple myeloma (MM) is a plasma cell dyscrasia characterized by the presence of multiple myelomatous "omas" throughout the skeleton, indicating that there is continuous trafficking of tumor cells to multiple areas in the bone marrow niches. MM may therefore represent one of the best models to study cell trafficking or cell metastasis. The process of cell metastasis is described as a multistep process, the invasion-metastasis cascade. This involves cell invasion, intravasation into nearby blood vessels, passage into the circulation, followed by homing into predetermined distant tissues, the formation of new foci of micrometastases, and finally the growth of micrometastasis into macroscopic tumors. This review discusses the significant advances that have been discovered in the complex process of invasion-metastasis in epithelial carcinomas and cell trafficking in hematopoietic stem cells and how this process relates to progression in MM. This progression is mediated by clonal intrinsic factors that mediate tumor invasiveness as well as factors present in the tumor microenvironment that are permissive to oncogenic proliferation. Therapeutic agents that target the different steps of cell dissemination and progression are discussed. Despite the significant advances in the treatment of MM, better therapeutic agents that target this metastatic cascade are urgently needed. IntroductionMultiple myeloma (MM) is a plasma cell dyscrasia characterized by the presence of multiple lytic lesions at the time of diagnosis. 1,2 The presence of multiple myelomatous "omas" throughout the axial skeleton detected at the time of diagnosis in most patients indicates that there is continuous spread or dissemination of tumor cells from the original site of tumor development to multiple sites in the BM niches, leading to the final development of symptomatic disease. Therefore, MM may represent a good model disease to study cell trafficking or cell metastasis. Although the term "metastasis" is not commonly used to describe dissemination of hematologic malignancies, this review attempts to examine how MM can use a process of cell dissemination that is similar to cell trafficking of hematopoietic stem cell (HSCs) and cell metastasis in solid epithelial carcinomas. These studies can guide our understanding of the biologic changes that occur during progression in MM. Cell metastasis and cell traffickingThe process of cell metastasis is usually described as a multistep process, often termed as the invasion-metastasis cascade. [3][4][5][6] This involves several steps of changes that include: (1) cell invasion, (2) intravasation (egress) into nearby blood vessels, (3) passage of the tumor cells into the circulation, followed by (4) homing or extravasation of tumor cells from these vessels into the specific predetermined distant tissues, (5) the formation of new foci of tumor micrometastases, and (6) finally the growth of micrometastatic lesions into macroscopic tumors, a step called "colonization."A similar process occurs with cell trafficking ...

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Monoclonal antibody-based therapy as a new treatment strategy in multiple myeloma

Cited by 73 publications

References 132 publications

Preclinical Evidence for the Therapeutic Potential of CD38-Targeted Immuno-Chemotherapy in Multiple Myeloma Patients Refractory to Lenalidomide and Bortezomib

Preclinical Evidence for the Therapeutic Potential of CD38-Targeted Immuno-Chemotherapy in Multiple Myeloma Patients Refractory to Lenalidomide and Bortezomib

Antibody-mediated phagocytosis contributes to the anti-tumor activity of the therapeutic antibody daratumumab in lymphoma and multiple myeloma

Myeloma as a model for the process of metastasis: implications for therapy

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