Daratumumab for the Treatment of Multiple Myeloma: A Review of Clinical Applicability and Operational Considerations

Arnall, Justin; Maples, Kathryn T.; Harvey, R. Donald; Moore, Donald C

doi:10.1177/10600280211058754

Cited by 12 publications

(7 citation statements)

References 53 publications

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“…Like for other monoclonal antibodies, infusion-related adverse reactions (IRRs), including upper respiratory symptoms (cough, throat irritation, nasal congestion, wheezing, or shortness of breath), chills, rash, and gastrointestinal symptoms, are the most common adverse events (AEs) in patients treated with DARA. 19,20 In our study, the incidence of IRRs was 27.27% in the standard infusion group and 1.35% in the rapid infusion group, which are comparable (p < 0.001). Our findings confirmed the results of the Barr et al 9 study, indicating the safety and feasibility of our regimen, which is consistent with the results of other studies.…”

Section: Discussionsupporting

confidence: 53%

Safety and feasibility analysis of rapid daratumumab infusion in Chinese patients with multiple myeloma

Yin,

Hu,

Yang

et al. 2024

Cancer Medicine

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BackgroundWith the increasing use of daratumumab (DARA)‐containing regimens for multiple myeloma (MM) patients in China, the standard infusion time of DARA is long, with the potential for infusion‐related reactions (IRRs) and increased hospitalization and use of resources. Shortening the duration of DARA infusion helps to optimize the hospital stay and enhance the patient treatment experience. The current, commonly used 90‐min rapid DARA infusion regimen may not be applicable to Chinese MM patients, and therefore, we explored a new 110‐min rapid DARA infusion regimen aimed at reducing the treatment burden on patients to guarantee therapeutic safety.MethodsMM inpatients treated with the DARA regimen were divided into two groups according to the number of times the DARA regimen was used: a standard infusion regimen for patients treated with the first two doses of DARA and a 110‐min rapid infusion regimen for patients treated with more than two doses of DARA. Anti‐allergy medications were routinely administered prior to the start of DARA infusion, patient consent, and authorization was obtained for all treatments, and statistical evaluation of the results was conducted via descriptive analyses, one‐way ANOVA and chi‐square tests.ResultsA total of 129 patients were included in this study: 68 in the standard infusion group, with 121 DARA infusions, and 129 in the rapid infusion group (patients who participated in the standard infusion subsequently participated in the rapid infusion), with 738 DARA infusions. The incidence of IRRs was 27.27% (36/121) in the standard infusion group and 1.35% (10/738) in the rapid infusion group, which were significantly different (p < 0.001). The incidence of IRRs after rapid infusion in other studies was <6%. The incidence of grade 1 IRRs in the rapid infusion group was 0.81% (6/738), the incidence of grade 2 IRRs was 0.54% (4/738), and there were no IRRs above grade 3; age, sex, and underlying disease had no effect on the choice of infusion method (p > 0.05). The mean infusion time after the occurrence of IRRs was also shorter in the rapid infusion group than in the standard infusion group (F = 24.781, p < 0.001).ConclusionThe 110‐min rapid infusion DARA regimen is feasible and safe for use in Chinese MM patients.

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Section: Discussionsupporting

confidence: 53%

Safety and feasibility analysis of rapid daratumumab infusion in Chinese patients with multiple myeloma

Yin,

Hu,

Yang

et al. 2024

Cancer Medicine

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“…The strength of this study is that we have investigated both TD and TI B-cell responses in the presence of DARA with a strong impact on TD stimulation and-in this respect-a differential outcome of different B-cell subsets, demonstrating the most impact of CD38 targeting on the activation and maturation of memory B cells into PBs and PCs. Although derived from an in vitro system, our findings do suggest a possible mechanism for the additional risk of bacterial and viral infections in MM patients receiving anti-CD38directed therapies in vivo (50,51). Where normally the barrier of immunological memory would protect patients, reduced recall responses by memory B cells upon TI or TD stimulation leave patients who receive DARA treatment prone to infections with common pathogens (16).…”

Section: Discussionmentioning

confidence: 83%

B-cell targeting with anti-CD38 daratumumab: implications for differentiation and memory responses

Verhoeven,

Grinwis,

Marsman

et al. 2023

Life Sci. Alliance

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B cell–targeted therapies, such as CD20-targeting mAbs, deplete B cells but do not target the autoantibody-producing plasma cells (PCs). PC-targeting therapies such as daratumumab (anti-CD38) form an attractive approach to treat PC-mediated diseases. CD38 possesses enzymatic and receptor capabilities, which may impact a range of cellular processes including proliferation and differentiation. However, very little is known whether and how CD38 targeting affects B-cell differentiation, in particular for humans beyond cancer settings. Using in-depth in vitro B-cell differentiation assays and signaling pathway analysis, we show that CD38 targeting with daratumumab demonstrated a significant decrease in proliferation, differentiation, and IgG production upon T cell–dependent B-cell stimulation. We found no effect on T-cell activation or proliferation. Furthermore, we demonstrate that daratumumab attenuated the activation of NF-κB in B cells and the transcription of NF-κB–targeted genes. When culturing sorted B-cell subsets with daratumumab, the switched memory B-cell subset was primarily affected. Overall, these in vitro data elucidate novel non-depleting mechanisms by which daratumumab can disturb humoral immune responses. Affecting memory B cells, daratumumab may be used as a therapeutic approach in B cell–mediated diseases other than the currently targeted malignancies.

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“…The binding of daratumumab with CD38 induces cell death through different Fc-mediated mechanisms: apoptosis, phagocytosis, and antibody- as well as complement-dependent cytotoxicity ( 27 ). Daratumumab causes an increase in the number of T cells in the bone marrow and blood, which results in a reinforcement of the immune response against malignant clonal cells ( 28 ). Based on the impressive results observed in several randomized phase III clinical trials ( 29 – 34 ), daratumumab is currently approved for the treatment of plasma cell tumors at different stages of the disease.…”

Section: Discussionmentioning

confidence: 99%

Daratumumab in the treatment of C3 glomerulopathy with monoclonal gammopathy: a case report and literature review

Esposito,

Picciotto,

Costigliolo

et al. 2023

Front. Med.

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Although rare, C3 glomerulopathy (C3G) is increasingly recognized thanks to the currently available diagnostic skills. C3G is not a single disease but a group of disorders with distinct pathogenesis and progression. Thus, an essential step for its management remains an in-depth characterization of the specific form and the identification of underlying conditions, which may also impact treatment choices as well. Among these entities, an emerging condition is the association of C3G with monoclonal gammopathy, which confers poor outcomes. Overall, diagnosis of C3G remains challenging, and determining the appropriate treatment remains unclear. Conventional immunosuppressive therapy has proven ineffective in such cases, while clone-directed therapies have shown promising results in small interventional studies and case series. Here, we report a case of a patient affected by C3G with monoclonal gammopathy of renal significance who experienced rapid deterioration of kidney function requiring replacement therapy. After the failure of first-line treatment, a switch to the anti-CD38 therapy with daratumumab resulted in the progressive improvement of the patient’s kidney function, leading to the discontinuation of hemodialysis after approximately 10 months. Serial renal biopsies were also performed to study the disease’s evolution in response to the treatment. Based on the description of this single case, we have comprehensively reviewed available studies on daratumumab use in patients with C3G associated with monoclonal gammopathy to provide insights for the design of prospective studies which aim to enhance the management of such poor prognosis disease.

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Daratumumab for the Treatment of Multiple Myeloma: A Review of Clinical Applicability and Operational Considerations

Cited by 12 publications

References 53 publications

Safety and feasibility analysis of rapid daratumumab infusion in Chinese patients with multiple myeloma

Safety and feasibility analysis of rapid daratumumab infusion in Chinese patients with multiple myeloma

B-cell targeting with anti-CD38 daratumumab: implications for differentiation and memory responses

Daratumumab in the treatment of C3 glomerulopathy with monoclonal gammopathy: a case report and literature review

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