Transfusion management for patients taking an anti-CD38 monoclonal antibody

Abstract

IntroductionPre-transfusion tests, essential for the release of blood components, may be affected by drugs. Monoclonal antibodies represent a class of medications increasingly used in the clinical practice, with anti-CD38 monoclonal antibodies (daratumumab) being a promising resource in the treatment of refractory myeloma. This monoclonal antibody recognizes CD38 in myeloma cells and interferes with pre-transfusion tests by causing panreactivity in indirect antiglobulin tests thereby clinically masking alloantibodies. Dithiothreitol is a reagent that breaks disulfide bonds and effectively destroys antigenic sites for CD38 on red blood cells. This study reports the immunohematological findings of pre-transfusion tests of patients with multiple myeloma receiving daratumumab and on solutions to prevent the interference of this monoclonal antibody.MethodsSerum samples from five patients on anti-CD38 monoclonal antibody treatment were evaluated. Tests performed included ABO/RhD typing, indirect antiglobulin test, direct antiglobulin test and eluate test. A daily evaluation was performed to determine the shelf life of dithiothreitol-treated red blood cells when stored in Alsever's solution.ResultsNo interference in the ABO/RhD typing results was noted but in all samples, a panreactivity was observed in indirect antiglobulin tests. Regarding the direct antiglobulin test, two samples presented positive results but negative eluates. In all samples, treatment of reagent red blood cells with 0.2 M dithiothreitol offset interference by anti-CD38 monoclonal antibodies. Dithiothreitol-treated red blood cells stored in Alsever's solution were stable for up to 15 days.ConclusionTreatment of reagent red blood cells with dithiothreitol can be efficient and accessible to offset the interference of the anti-CD38 drug in pre-transfusion tests. The number of costly serological workups can be reduced by having stored dithiothreitol red blood cells with this proving to be a useful reagent for investigating anti-CD38.

The role of the Kidd-antibodies in posttransfusion reactions

“…Phenotyping may be inaccurate if a patient has received a blood transfusion in the previous 3 months [39,40]. In this case, the genotype is unaff ected, and blood group genotyping is the method of choice [22,41,42].…”

A stressful predicament for blood bankers!

“…Some of these antibodies recognise red blood cells (RBCs) as well as their intended cancer cell targets and can create considerable havoc in transfusion services when trying to provide compatible blood for transfusion to those patients who are receiving these medications . Anti‐CD38 (daratumumab; DARA) is one example that has been used for a few years now and is FDA approved for use in multiple myeloma patients; unfortunately, it causes panagglutination in serologic tests . The good news is that these serologic reactions are relatively weak (1+ to 2+), and various ways have been reported around the anti‐CD38 panagglutination, enabling elucidation of potentially clinically significant underlying alloantibodies .…”

“…The good news is that these serologic reactions are relatively weak (1+ to 2+), and various ways have been reported around the anti‐CD38 panagglutination, enabling elucidation of potentially clinically significant underlying alloantibodies . These various approaches include the use of dithiothreitol (DTT) and other means to work around this issue and allow more assurances that no potentially clinically significant alloantibodies underly the panagglutination …”

Immunotherapy: the good, the bad, the ugly, and the really ugly

“…Both of these methods may be set up in larger reference laboratories but are not practical for more routine blood transfusion services. Thus, it was found that dithiothreitol (DTT) could be used to treat reference screening and/or panel RBCs and that this DTT treatment would denature the CD38 allowing for subsequent alloantibody investigation . Although this is a method with a history of use in transfusion medicine, DTT treatment at the normal concentration used (0.2 M) can denature additional RBC antigens that could possibly result in missing some clinically significant alloantibodies, especially to high‐prevalence antigens, such those in the Kell blood group system or Cartwright system (i.e., anti‐Yt a ) .…”

“…The article by Velliquette et al paints a picture of the serologic problems that are likely to be encountered when testing patients, not only those receiving anti‐CD38 or anti‐CD47 therapy, but likely what future serology would look like if/when other immunotherapeutics that cross react with RBCs come to fruition . A recurring theme in these reports is that it will be difficult to determine underlying alloantibodies of potential clinical significance in the presence of these therapeutic antibodies.…”