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Multiple myeloma, gammopaths

Ninety-minute daratumumab infusion is safe in multiple myeloma

Leukemia volume 32, pages 2495–2518 (2018)Cite this article

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Daratumumab is a first-in-class anti-CD38 moantibody approved for relapsed and refractory multiple myeloma [1, 2] and being tested in both smoldering [3] and newly diagnosed myeloma [4]. CD38 is expressed on airway smooth muscle cells, and infusion related reactions (IRRs) were marked by symptoms (cough, wheezing, and rhinorrhea) similar to those of allergic rhinitis. Of all patients treated at 8 and 16 mg/kg in two pivotal trials, the proportion of patients that suffered an IRR was 65% (grade 1–2) and 3% (grade 3–4) in the GEN501 trial [1], and 59% (grade 1–2) and 4% (grade 3–4) in the SIRIUS trial [2]. A pooled analysis of SIRIUS and GEN501 data demonstrated that most IRRs (95.8%) occur during the first infusion, with a decreased incidence of IRRs during second (7%) and subsequent infusions (7%) [5]. There is no relationship between daratumumab serum levels and the development of IRRs [6].

The incidence and severity of IRRs has led to the recommended administration rates which result in infusion times for the first, second, and subsequent infusions of 6.5, 4.5, and 3.5 h, respectively [7]. To decrease the IRR rate, one trial tested the addition of 10 mg of montelukast as a premedication prior to the first daratumumab infusion and found the IRR rate was one-third lower in patients who received this leukotriene inhibitor [8]. Beyond slowing the infusion rate, no other clinical trial has successfully reported any intervention to decrease the IRR rate [9].

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Acknowledgements

Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under Award Number P30CA016058. The content is solely the responsibility of the authors and does not represent the official views of the National Cancer Institute or the National Institutes of Health.

Author contributions

HB and CCH wrote the protocol and the manuscript. YH designed the statistics. HB, JD, and AW enrolled patients. HB, NS, NW, and CCH prepared case report forms. Data analysis was performed by HB, NS, and NW. All authors reviewed and approved the final manuscript.

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Authors and Affiliations

  1. Wexner Medical Center, Ohio State University, Columbus, OH, USA

    Hallie Barr, Jessica Dempsey & Allyson Waller

  2. Department of Internal Medicine, Division of Hematology, Ohio State University, Columbus, OH, USA

    Ying Huang, Don M. Benson, Ashley E. Rosko, Yvonne A. Efebera & Craig C. Hofmeister

  3. Comprehensive Cancer Center, Ohio State University, Columbus, OH, USA

    Nita Williams & Nidhi Sharma

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  1. Hallie Barr
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Correspondence to Hallie Barr.

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Conflict of interest

DMB, CCH, YAE, and AER obtained research funding from Celgene, Janssen, Takeda, Roche, Karyopharm, Bristol-Myers Squibb; CCH participated in advisory board for Celgene, Adaptive Biotechnologies. Other authors declare that they have no conflict of interest.

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Barr, H., Dempsey, J., Waller, A. et al. Ninety-minute daratumumab infusion is safe in multiple myeloma. Leukemia 32, 2495–2518 (2018). https://doi.org/10.1038/s41375-018-0120-2

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