Daratumumab-based induction therapy for multiple myeloma: A systematic review and meta-analysis

Chong, Lip Leong; Soon, Yu Yang; Soekojo, Cinnie Yentia; Ooi, Melissa; Chng, Wee Joo; Mel, Sanjay de

doi:10.1016/j.critrevonc.2020.103211

Cited by 19 publications

(16 citation statements)

References 19 publications

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“…treatment of R/R MM patients [30,[34][35][36]. Recently, a new formulation of DARA conta ing recombinant human hyaluronidase PH20 has become available that can be admin tered subcutaneously [37].…”

Section: Rationale Of Targeting Cd38 Slamf7 Cd137 and Kir As An Immunomodulatory Strategy Against Immunosuppressive Tme In MMmentioning

confidence: 99%

“…CD38 surface antigen is abundantly expressed on MM cells [ 30 , 34 , 35 ]. Anti-CD38 MoAb, including daratumumab (DARA), isatuximab (ISA), and MOR202 ( Figure 2 ), have shown tolerability as well as meaningful clinical activity in FDA-approved monotherapy regimens and as components of FDA-approved multi-modality combination regimens for treatment of R/R MM patients [ 30 , 34 , 35 , 36 ]. Recently, a new formulation of DARA containing recombinant human hyaluronidase PH20 has become available that can be administered subcutaneously [ 37 ].…”

Section: Rationale Of Targeting Cd38 Slamf7 Cd137 and Kir As An Immunomodulatory Strategy Against Immunosuppressive Tme In MMmentioning

confidence: 99%

“…Mechanisms of primary and/or acquired resistance include tumor-related factors. It has been shown that increased expression levels of complement inhibitors CD55 and CD59 as well as decreased cell surface expression levels of CD38 on MM cells may confer resistance to anti-CD38 MoAb [ 35 ], whereas certain KIR and HLA genotypes are associated with higher effectiveness of treatment regimens employing anti-CD38 MoAb [ 35 ]. Therefore, biomarker-guided patient-tailored application of anti-CD38 MoAb may further improve their clinical impact potential in MM therapy.…”

Section: Rationale Of Targeting Cd38 Slamf7 Cd137 and Kir As An Immunomodulatory Strategy Against Immunosuppressive Tme In MMmentioning

confidence: 99%

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Overcoming the Immunosuppressive Tumor Microenvironment in Multiple Myeloma

Uckun

2021

Cancers

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SeverFigurel cellular elements of the bone marrow (BM) microenvironment in multiple myeloma (MM) patients contribute to the immune evasion, proliferation, and drug resistance of MM cells, including myeloid-derived suppressor cells (MDSCs), tumor-associated M2-like, “alternatively activated” macrophages, CD38+ regulatory B-cells (Bregs), and regulatory T-cells (Tregs). These immunosuppressive elements in bidirectional and multi-directional crosstalk with each other inhibit both memory and cytotoxic effector T-cell populations as well as natural killer (NK) cells. Immunomodulatory imide drugs (IMiDs), protease inhibitors (PI), monoclonal antibodies (MoAb), adoptive T-cell/NK cell therapy, and inhibitors of anti-apoptotic signaling pathways have emerged as promising therapeutic platforms that can be employed in various combinations as part of a rationally designed immunomodulatory strategy against an immunosuppressive tumor microenvironment (TME) in MM. These platforms provide the foundation for a new therapeutic paradigm for achieving improved survival of high-risk newly diagnosed as well as relapsed/refractory MM patients. Here we review the scientific rationale and clinical proof of concept for each of these platforms.

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Section: Rationale Of Targeting Cd38 Slamf7 Cd137 and Kir As An Immunomodulatory Strategy Against Immunosuppressive Tme In MMmentioning

confidence: 99%

Section: Rationale Of Targeting Cd38 Slamf7 Cd137 and Kir As An Immunomodulatory Strategy Against Immunosuppressive Tme In MMmentioning

confidence: 99%

Section: Rationale Of Targeting Cd38 Slamf7 Cd137 and Kir As An Immunomodulatory Strategy Against Immunosuppressive Tme In MMmentioning

confidence: 99%

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Overcoming the Immunosuppressive Tumor Microenvironment in Multiple Myeloma

Uckun

2021

Cancers

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“…First came the monoclonal antibodies (mAbs), which represented a paradigm shift in treating all MM stages [ 3 , 4 , 5 , 6 , 7 ]. The initial mAbs included daratumumab, which targets CD38 on MM cells’ surface [ 8 , 9 ], and elotuzumab, which targets SLAMF7 [ 10 ]. These new molecules were followed by isatuximab, which also targets CD38 [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

CART-Cell Therapy: Recent Advances and New Evidence in Multiple Myeloma

Martino

Canale

Alati

et al. 2021

Cancers

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Despite the improvement in survival outcomes, multiple myeloma (MM) remains an incurable disease. Chimeric antigen receptor (CAR) T-cell therapy targeting B-cell maturation antigen (BCMA) represents a new strategy for the treatment of relapsed/refractory MM (R/R). In this paper, we describe several recent advances in the field of anti-BCMA CAR T-cell therapy and MM. Currently, available data on anti-BCMA CART-cell therapy has demonstrated efficacy and manageable toxicity in heavily pretreated R/R MM patients. Despite this, the main issues remain to be addressed. First of all, a significant proportion of patients eventually relapse. The potential strategy to prevent relapse includes sequential or combined infusion with CAR T-cells against targets other than BCMA, CAR T-cells with novel dual-targeting vector design, and BCMA expression upregulation. Another dark side of CART therapy is safety. Cytokine release syndrome (CRS) andneurologic toxicity are well-described adverse effects. In the MM trials, most CRS events tended to be grade 1 or 2, with fewer patients experiencing grade 3 or higher. Another critical point is the extended timeline of the manufacturing process. Allo-CARs offers the potential for scalable manufacturing for on-demand treatment with shorter waiting days. Another issue is undoubtedly going to be access to this therapy. Currently, only a few academic centers can perform these procedures. Recognizing these issues, the excellent response with BCMA-targeted CAR T-cell therapy makes it a treatment strategy of great promise.

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“…MM is the second-most common hematologic malignancy. Although the drug store has grown significantly in the last few years, there are no definitive curative actions for MM, so it is particularly important to develop new chemotherapeutic agents with new mechanisms of action [10][11][12][13][14]. Among these works, there is also our research recently published in this journal [15].…”

Section: Introductionmentioning

confidence: 99%

Untitled

2021

Biointerface Res Appl Chem

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Many reports have documented the role of INS (insulin) as growth factors in a variety of cancers. Epidemiological studies revealed that INS therapy causes increased mortality in multiple myeloma (MM) patients with pre-existing or steroid-induced type 2 diabetes. However, there is limited experimental evidence of this association. In the present study, the dual effect of INS on the viability of myeloma RPMI8226 and lymphoblastoid IM9 cells was revealed. In serum-containing medium exogenous INS serves as a growth factor, whereas INS decreases the number of cells under serum-free medium. In the last case, the main mechanism of decreasing the cell population is apoptosis through up-regulation of Cas-3 and downregulation of Bcl-2 expression. INS has also been shown to be involved in the regulation of necrotic cell death.

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Daratumumab-based induction therapy for multiple myeloma: A systematic review and meta-analysis

Cited by 19 publications

References 19 publications

Overcoming the Immunosuppressive Tumor Microenvironment in Multiple Myeloma

Overcoming the Immunosuppressive Tumor Microenvironment in Multiple Myeloma

CART-Cell Therapy: Recent Advances and New Evidence in Multiple Myeloma

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