Ninety-minute daratumumab infusion is safe in multiple myeloma

Barr, H; Dempsey, Jessica; Waller, Allyson; Huang, Ying; Williams, Nita; Sharma, Nidhi; Benson, Don M.; Rosko, Ashley; Efebera, Yvonne A.; Hofmeister, Craig C.

doi:10.1038/s41375-018-0120-2

Cited by 54 publications

(70 citation statements)

References 16 publications

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“…Previous experience with infusing monoclonal antibodies over a shorter time led to the hypothesis that infusing daratumumab over 90 minutes, starting with the third infusion, would not increase the proportion of IRs . This protocol focused on patients who had already received 2 or more daratumumab infusions because the risk of grade 3 to 4 infusion‐related reactions had been very small in trials reported to date . Starting with the first dose on protocol, we infused 20% of the dose over 30 minutes and then 80% over 60 minutes for a total duration of 1.5 hours; this saved an estimated 2 hours.…”

Section: Managing Daratumumab‐related Toxicities and Practical Aspectsmentioning

confidence: 99%

“…At the 4‐week follow‐up point, all patients remained on the accelerated infusion with no additional toxicities. The only AE was 1 case of grade 2 hypertension, which occurred with the 450 mL/h rate and then subsequently resolved after a return to the 200 mL/h rate and the administration of a diuretic …”

Section: Managing Daratumumab‐related Toxicities and Practical Aspectsmentioning

confidence: 99%

“…34 This protocol focused on patients who had already received 2 or more daratumumab infusions because the risk of grade 3 to 4 infusion-related reactions had been very small in trials reported to date. 35 Starting with the first dose on protocol, we infused 20% of the dose over 30 minutes and then 80% over 60 minutes for a total duration of 1.5 hours; this saved an estimated 2 hours. The rate was initially 200 mL/h (30 minutes) and then 450 mL/h (60 minutes).…”

Section: -Minute Daratumumab Infusionmentioning

confidence: 99%

“…The only AE was 1 case of grade 2 hypertension, which occurred with the 450 mL/h rate and then subsequently resolved after a return to the 200 mL/h rate and the administration of a diuretic. 35 Our current premedication strategy involves pruning the regimen to simply intravenous dexamethasone Cancer July 15, 2019 or methylprednisolone from the third 90-minute dosing onward. Our current practice avoids testing accelerated daratumumab in any patient whose most recent dose was prepared in the 1000-mL dilution because of moderate or severe IRs.…”

Section: -Minute Daratumumab Infusionmentioning

confidence: 99%

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Daratumumab in multiple myeloma

Nooka

Kaufman

Hofmeister

et al. 2019

Cancer

Self Cite

104

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The development of effective monoclonal antibodies for the treatment of myeloma has been a long journey of clinical and drug development. Identification of the right target antigen was a critical part of the process. CD38 as a target has been considered for some time, but clinically, daratumumab, a CD38 monoclonal antibody, was the first to be tested, and it has delivered the best clinical responses as a single agent to date. Its proven safety and efficacy in combination with other antimyeloma agents have led to several US Food and Drug Administration approvals for treating myeloma. Furthermore, the results of early trials in the induction therapy setting have demonstrated a beneficial role when it is added to the existing induction regimens. This review summarizes the importance of CD38 as a target and examines the clinical development of the CD38 monoclonal antibody daratumumab and its clinical significance in combination regimens in both patients with relapsed/refractory myeloma and patients with newly diagnosed myeloma.

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Section: Managing Daratumumab‐related Toxicities and Practical Aspectsmentioning

confidence: 99%

Section: Managing Daratumumab‐related Toxicities and Practical Aspectsmentioning

confidence: 99%

Section: -Minute Daratumumab Infusionmentioning

confidence: 99%

Section: -Minute Daratumumab Infusionmentioning

confidence: 99%

See 2 more Smart Citations

Daratumumab in multiple myeloma

Nooka

Kaufman

Hofmeister

et al. 2019

Cancer

Self Cite

104

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show abstract

“…One of the limitations to the use of daratumumab is its long infusion time (3.5 h). To deal with this issue, a shorter infusion schedule was tested-daratumumab was administered over a 90 min infusion at the usual dose (16 mg/kg) from the third infusion onward, without increasing the risk for infusion-related reactions (IRRs) or further short-term AEs [54]. A game changer in this setting will be the possibility of delivering daratumumab subcutaneously over a short period of time.…”

Section: Daratumumabmentioning

confidence: 99%

Therapeutic Monoclonal Antibodies and Antibody Products: Current Practices and Development in Multiple Myeloma

Bonello

Mina

Boccadoro

2019

Cancers

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Immunotherapy is the latest innovation for the treatment of multiple myeloma (MM). Monoclonal antibodies (mAbs) entered the clinical practice and are under evaluation in clinical trials. MAbs can target highly selective and specific antigens on the cell surface of MM cells causing cell death (CD38 and CS1), convey specific cytotoxic drugs (antibody-drug conjugates), remove the breaks of the immune system (programmed death 1 (PD-1) and PD-ligand 1/2 (L1/L2) axis), or boost it against myeloma cells (bi-specific mAbs and T cell engagers). Two mAbs have been approved for the treatment of MM: the anti-CD38 daratumumab for newly-diagnosed and relapsed/refractory patients and the anti-CS1 elotuzumab in the relapse setting. These compounds are under investigation in clinical trials to explore their synergy with other anti-MM regimens, both in the front-line and relapse settings. Other antibodies targeting various antigens are under evaluation. B cell maturation antigens (BCMAs), selectively expressed on plasma cells, emerged as a promising target and several compounds targeting it have been developed. Encouraging results have been reported with antibody drug conjugates (e.g., GSK2857916) and bispecific T cell engagers (BiTEs ® ), including AMG420, which re-directs T cell-mediated cytotoxicity against MM cells. Here, we present an overview on mAbs currently approved for the treatment of MM and promising compounds under investigation.Cancers 2020, 12, 15 2 of 24 Cancers 2020, 12, 15 3 of 24 (Bregs, which promote tumor growth and immune escape), as well as a subset of regulatory T cells (Tregs) express CD38, and their levels are reduced after daratumumab exposure. Conversely, daratumumab results in significant expansion of CD8+ cytotoxic and CD4+ helper T cells, likely following the depletion of regulatory cells. Remarkably, expanded effector T cells also show increased killing capacity due to augmented levels of granzyme B, which activates caspases and triggers cell apoptosis [23][24][25]. In addition, among the activities promoted by CD38, there is a nicotinamide adenine dinucleotide (NAD)-ase activity, which results in reduced levels of NAD+ in T cells, responsible for the loss of their effector functions (exhausted T cells). In murine models, anti-CD38 mAbs administration induced higher levels of NAD+ in T effector cells, thus enhancing their antitumor activity [23]. The main mechanisms of action of anti-CD38 monoclonal antibodies are summarized in Figure 1.

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Plasma Cell Disorders

Yee¹,

Hideshima²,

Raje³

et al. 2022

Holland‐Frei Cancer Medicine

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Overview Plasma cell disorders have in common a proliferation of monoclonal plasma cells associated with the production of a monoclonal protein. These disorders range from the common, indolent condition of monoclonal gammopathy of undetermined significance to malignancies such as multiple myeloma characterized by the presence of hypercalcemia, anemia, renal dysfunction, and/or lytic bone lesions. Progress in the understanding of the molecular underpinnings of myeloma has led to remarkable advances in its treatment. High‐dose melphalan and autologous stem cell transplant have been a mainstay of treatment. Now, highly effective and well‐tolerated drug classes such as the proteasome inhibitors (e.g., bortezomib, carfilzomib), immunomodulatory drugs (e.g., lenalidomide, pomalidomide), and anti‐CD38 monoclonal antibodies (e.g., daratumumab, isatuximab) have rapidly transformed treatment and significantly improved overall survival. Newer therapies targeting B‐cell maturation antigen (BCMA) have the potential to further improve outcomes.

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Ninety-minute daratumumab infusion is safe in multiple myeloma

Cited by 54 publications

References 16 publications

Daratumumab in multiple myeloma

Daratumumab in multiple myeloma

Therapeutic Monoclonal Antibodies and Antibody Products: Current Practices and Development in Multiple Myeloma

Plasma Cell Disorders

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