Mitigation of therapeutic <scp>anti‐CD38</scp> antibody interference with fab fragments: How well does it perform?

Habicht, Cora P.; Ridders, Michael; Grueger, Daniela; Adolph, Svenja; Immenschuh, Stephan; Schneeweiß, Clemens

doi:10.1111/trf.17253

Cited by 3 publications

(2 citation statements)

References 17 publications

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“…Even better results were achieved by Habicht and colleagues, who reported that DaraEx ® effectively mitigated the interference caused by anti-CD38 antibodies in 86% of patient samples tested, while DTT was successful in only 68% of cases. They also emphasized that unlike DTT, DaraEx ® does not negatively impact sensitive blood group systems (7).…”

Section: Discussionmentioning

confidence: 99%

“…To eliminate interference, we used a specific DaraEx ® reagent that utilizes Fab fragments of anti-CD38 to mitigate interference by masking CD38 on the cell surface. This approach avoids nonspecific panreactivity and neutralizes anti-CD38 (7). Subsequent application of this reagent resulted in negative IAT results for all three patients (Figure 2).…”

Section: Case Reportmentioning

confidence: 99%

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The importance of removing interference caused by Darzalex® (daratumumab) in pre-transfusion testing

Dilberović,

Kola,

Kola

2024

JHSCI

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Introduction: Multiple myeloma (MM) is a hematologic malignacy characterized by the uncontrolled proliferation of abnormal plasma cells in the bone marrow. Darzalex® (daratumumab) has emerged as a highly effective therapeutic agent for MM, offering an additional treatment option for patients who have developed resistance to other therapies. However, the use of Darzalex® poses challenges in pre-transfusion testing due to its strong binding affinity of the monoclonal anti-CD38 antibody to CD38 protein, resulting in panreactivity with test erythrocytes and complicating the detection of erythrocyte alloantibodies. The objective of this case report is to outline the procedures, significance, and methodologies for mitigating this interference using the DaraEx® reagent. Case Report: We present the cases of three patients diagnosed with MM and treated with Darzalex® at our institution in 2023. Following the administration of Darzalex®, all three patients exhibited positive results on indirect antiglobulin tests (IAT). Cross-matching tests conducted with red blood cell concentrates also yielded positive results, with strengths ranging from 2+ to 3+. To eliminate interference, we used a specific DaraEx® reagent that utilizes Fab fragments of anti-CD38 to mitigate interference by masking CD38 on the cell surface. Subsequent application of this reagent resulted in negative IAT results for all three patients. However, one patient still displayed a weakly positive cross-matching test (<1+), suggesting that complete elimination of interference may not always be achievable with the DaraEx® method. Conclusion: Despite the availability of reliable methods such as dithiothreitol and the DaraEx® reagent for mitigating interference, complete success in eliminating interference remains elusive. This underscores the importance of implementing proactive measures to prevent interference. Patients undergoing Darzalex® therapy should undergo comprehensive immunohematological testing before medication administration. Given the increased need for blood transfusions in MM patients, ensuring the compatibility of blood products is essential for safe transfusion practices.

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Section: Discussionmentioning

confidence: 99%

Section: Case Reportmentioning

confidence: 99%

The importance of removing interference caused by Darzalex® (daratumumab) in pre-transfusion testing

Dilberović,

Kola,

Kola

2024

JHSCI

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Risk of new alloimmunization in patients on anti-CD38 treatment using tube LISS-IAT method

Safić Stanić,

Kruhonja Galić,

Lukić

et al. 2024

Transfusion and Apheresis Science

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Is drug interference still an issue for pretransfusion testing of patients on anti CD38 and other monoclonal antibody therapies?

Bevel,

Thorpe,

Vanniasinkam

2024

Vox Sanguinis

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Certain therapies that target CD markers on some blood cells can affect pretransfusion testing. Key examples are anti‐CD38, CD47 monoclonal antibody (mAb) therapies such as daratumumab (DARA) and magrolimab, which have presented a challenge for transfusion medicine laboratories around the globe. Scientists have been faced with not only introducing a protocol to provide safe blood to patients but also investigating the most effective method to remove the pretransfusion pan‐agglutinating interference caused. A number of papers in the last 5 years have reported on various methods to remove pretransfusion interference; however, most of these studies have been conducted only in a few countries. Most recent reviews on this topic have focused on techniques and reagents to remove pretransfusion interference, and dithiothreitol is currently the gold standard for removing DARA interference. However, it was clear from this review that while many laboratories have developed processes for addressing interference in pretransfusion testing, and DARA interference may not be a major issue, there are still laboratories around the world, that may not have adequately addressed this issue. In addition, the impact of mAb interference on widely used techniques such as flow cytometry is unclear.

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Mitigation of therapeutic anti‐CD38 antibody interference with fab fragments: How well does it perform?

Cited by 3 publications

References 17 publications

The importance of removing interference caused by Darzalex® (daratumumab) in pre-transfusion testing

The importance of removing interference caused by Darzalex® (daratumumab) in pre-transfusion testing

Risk of new alloimmunization in patients on anti-CD38 treatment using tube LISS-IAT method

Is drug interference still an issue for pretransfusion testing of patients on anti CD38 and other monoclonal antibody therapies?

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