F(ab′)
            <sub>2</sub>
            Fragments to Overcome Daratumumab Interference in Transfusion Tests

Selleng, Kathleen; Gebicka, Patrycja; Thiele, Thomas

doi:10.1056/nejmc1804751

Cited by 21 publications

(19 citation statements)

References 4 publications

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“…This need will become even more acute with the development of new CD38‐specific antibodies or antibodies against other common antigens and membrane proteins expressed on RBCs (e.g., anti‐CD47), which are currently being evaluated in clinical trials. The development of a feasible and affordable method to selectively neutralize or remove DARA from a patient's plasma is desirable to permit a valuable IAT in immunized patients . The fact that CD38 antigen is destroyed by DTT without destroying many other RBC antigens is fortuitous for DARA, but this approach will not address future targeted therapies, such as anti‐CD47 .…”

Section: Discussionmentioning

confidence: 99%

“…The development of a feasible and affordable method to selectively neutralize or remove DARA from a patient's plasma is desirable to permit a valuable IAT in immunized patients. 18 The fact that CD38 antigen is destroyed by DTT without destroying many other RBC antigens is fortuitous for DARA, but this approach will not address future targeted therapies, such as anti-CD47. 27,28 The emergence of these novel humanized monoclonal antibodies with possible unintended or off-target binding of RBCs in blood bank reagents remains a serious challenge and cost consideration.…”

Section: Discussionmentioning

confidence: 99%

“…Alternatively, trypsin‐treated reagent RBCs or RBCs that are negative for CD38 (RBCs from DARA patients or In(Lu) RBCs) can also be used for antibody investigations . Finally, anti‐CD38 idiotype antibodies, soluble CD38, cord blood cell antibody panels, and F(ab′) 2 fragments can also be utilized to mitigate DARA interference; however, these reagents are not commercially available. Others have advocated for phenotype matching without antibody investigation in patients known to be on DARA to simplify and expedite testing …”

mentioning

confidence: 99%

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The impact of Daratumumab on transfusion service costs

et al. 2019

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BACKGROUND Daratumumab (DARA) is a human IgG1κ monoclonal antibody directed against CD38, approved for the treatment of multiple myeloma. As CD38 is expressed on RBCs, DARA can interfere with pretransfusion testing. DARA interference can be negated by denaturation of CD38 on RBCs with dithiothreitol (DTT) reagents. Because of this interference in pretransfusion testing, our hospital implemented a notification and testing/transfusion algorithm (NATTA) for pretransfusion testing and RBC product provision for DARA patients. This standardized approach combines DTT‐based testing with selective genotyping and the provision of phenotypically similar RBCs for patients with clinically significant antibodies. STUDY DESIGN AND METHODS We evaluated pretransfusion test results and transfusion requirements for 91 DARA patients in an academic medical center over 1 year to determine the incremental cost of pretransfusion testing and RBC selection. The actual costs for the NATTA approach were compared to a theoretical approach using universal genotyping with a provision of phenotypically similar RBC transfusions. RESULTS The annual cost of testing related to DARA after NATTA implementation was $535.76 per patient. The simulated annual cost for the alternative genotyping with provision of phenotypically similar RBC transfusions approach was $934.83 per patient. CONCLUSION In our entire cohort of DARA patients, a DTT‐based testing algorithm with selective genotyping and provision of phenotypically similar RBCs only for patients with clinically significant antibodies was less expensive than a simulated model of universal genotyping and provision of phenotypically similar RBCs.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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The impact of Daratumumab on transfusion service costs

et al. 2019

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“…Specific strategies may be used in daratumamab-treated patients to prevent antibody binding such as dithiothreitol (DTT) treatment of reagent RBCs or the use of F(ab 0 ) 2 fragments to block drug binding to the CD38 epitope. 14,15 For anti-CD47, use of multiple alloadsorptions and monoclonal gamma-clone anti-IgG, which does not detect IgG4, have been proposed to help mitigate antibody interference. 16 In the Phase 1b study of Hu5F9-G4 in relapsed/ refractory B-NHL, anemia occurred in approximately 42% of patients.…”

Section: Resultsmentioning

confidence: 99%

The effects of monoclonal anti‐CD47 on RBCs, compatibility testing, and transfusion requirements in refractory acute myeloid leukemia

et al. 2019

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“…More recently, daratumumab F(ab′)2 fragments have demonstrated efficacy in abrogating daratumumab interference through competitive inhibition for the CD38 antigen. 43 For blood banks that do not routinely use DTT or do not have access to the aforementioned interference-mitigating reagents, red blood cell phenotyping and providing phenotypically matched blood are recommended. 42,44 In cases of recent transfusions, red blood cell genotyping and providing genotypically matched cells constitute an alternative approach.…”

Section: Daratumumab Interferencementioning

confidence: 99%

Daratumumab in multiple myeloma

Nooka

Kaufman

Hofmeister

et al. 2019

Cancer

114

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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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F(ab′) ₂ Fragments to Overcome Daratumumab Interference in Transfusion Tests

Cited by 21 publications

References 4 publications

The impact of Daratumumab on transfusion service costs

The impact of Daratumumab on transfusion service costs

The effects of monoclonal anti‐CD47 on RBCs, compatibility testing, and transfusion requirements in refractory acute myeloid leukemia

Daratumumab in multiple myeloma

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F(ab′) 2 Fragments to Overcome Daratumumab Interference in Transfusion Tests

Cited by 21 publications

References 4 publications

The impact of Daratumumab on transfusion service costs

The impact of Daratumumab on transfusion service costs

The effects of monoclonal anti‐CD47 on RBCs, compatibility testing, and transfusion requirements in refractory acute myeloid leukemia

Daratumumab in multiple myeloma

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Product

Resources

About

F(ab′) ₂ Fragments to Overcome Daratumumab Interference in Transfusion Tests