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Daratumumab Interferes with Antibody Screen

June 13, 2023

Gausan Ratna Bajracharya, MD; Alparslan Turan, MD

Multiple Myeloma Plasma Cell Malignancy

Multiple myeloma is a plasma cell malignancy often presenting with severe anemia. These patients are at risk of developing new antibodies to red cell antigens because of frequent blood transfusions. The purpose of this letter is to raise awareness about the interference of routine pre-transfusion antibody screening by Daratumumab (DARA), a common drug used to treat multiple myeloma. We will also provide some recommendations for perioperative management of these patients.

Daratumumab (DARA), a CD38-antibody, is one of several new antibody-based cancer therapies for multiple myeloma. DARA causes pan-agglutination in antibody screening resulting in an inability to identify the presence of antibodies for safe transfusion. 1 Pan-agglutination occurs because CD38 antigen highly expressed in myeloma cells is also expressed on normal human RBCs. In some cancer patients, this expression may even increase.2 In order to get an updated antibody screen, practitioners should check with their local laboratory for the ability to perform a post-DARA antibody screen. Laboratories without access to advanced in-house testing are required to send a sample to a reference laboratory for testing which may take 24-48 hours to result. These labs use a special reagent called dithiothreitol (DTT) to destroy CD-38 antigens in red-cells to get rid of this interference. The DTT method can allow detection of antibodies to other red cell antigens such as Rh, Duffy, Kidd, and MNSs in order to prevent major clinically significant hemolytic reactions. The disadvantage of using DTT for this purpose is that it also destroys other red cell antigens including Kell, Dombrock, Indian, John Milton Hagen, Knops, Landsteiner-Wiener, Lutheran, Raph and Cartwright.1,3 Among these DTT-sensitive blood group systems, anti-K (Kell) is the most commonly encountered and clinically significant antibody which can result in immediate or delayed mild to severe transfusion reactions.

DARA has not been shown to cause significant hemolysis1 despite binding to all red cells. After correctly identifying presence of atypical antibodies with the post-DARA screen using DTT, blood banks can release appropriate units of red cells from donors who are negative for the K1 antigen in the Kell system. Thankfully, 90% of units donated to blood banks are K1-antigen negative.4 However, blood banks will require to release these units under exceptional release because cross matching to appropriate units will still result in agglutination resulting from DARA. During emergencies, when anesthesia professionals cannot wait 24-48 hours to transfuse (e.g., major trauma, unanticipated and massive intraoperative bleeding, etc.), group O units with appropriate Rh type are still a viable option to transfuse in these patients. Meanwhile, requests to expedite antibody screening can be processed on a case-by-case basis after communicating with the reference labs.

In conclusion, anesthesia professionals must keep a watch for patients with multiple myeloma, and check if they have been treated with DARA. Persistent pan-agglutination reactions in antibody screen can be seen up to 6 months after stopping this medication. Practitioners will want to be aware of other upcoming antibody-based cancer therapies at various stages of development, that may similarly interfere with routine blood bank tests. Examples include anti-CD38 (isatuximab) and anti-CD47 (magrolimab, lemzoparlimab, evorpacept).

 

Gausan Ratna Bajracharya is an Associate Staff in the Department of General Anesthesiology, Anestheisology Institute, Cleveland Clinic Foundation

Alparslan Turan is a Professor of Anesthesia in the Department of Outcomes Research, Anesthesiology Institute, Cleveland Clinic Foundation

The authors have no conflicts of interest.

REFERENCES

  1. Chapuy CI, Aguad MD, Nicholson RT, et al. International validation of a dithiothreitol (DTT)-based method to resolve the daratumumab interference with blood compatibility testing. American Society of Hematology Washington, DC; 2015.
  2. Albeniz I, Demir Ö, Türker-Şener L, Yalçintepe L, Nurten R, Bermek E. Erythrocyte CD38 as a prognostic marker in cancer. Hematology. 2007;12(5):409-414.
  3. Roback J, Grossman B, Harris T, Hillyer C. Technical manual. 17th edBethesda. MD: AABB Press; 2011.
  4. Reid ME, Lomas-Francis C, Olsson ML. The blood group antigen factsbook. Academic press; 2012.