Impact of new myeloma agents on the transfusion laboratory

Monoclonal antibody (mAb) therapy targeting CD38 and CD47 antigens expressed on cancer cells has transformed therapy options for patients with multiple myeloma as well as other haematological and non-haematological malignancies. While the on target effects of these new drugs highlight the promise of precision cancer therapeutics, the unintended, off target binding of drugs to red blood cells (RBCs) and platelets has required transfusion service laboratories (TSL) and immunohaematology reference laboratories (IRL) to innovate and rapidly set up processes and testing protocols to overcome the significant interference in routine pre-transfusion tests caused by these agents. Binding of anti-CD38 and anti-CD47 drugs to reagent RBCs leads to false positive pan-agglutination during the antihuman globulin phase of testing, making it difficult to rule out underlying alloantibodies, and leading to delays in setting up compatible units for RBC transfusion. Anti-CD47 agents can also interfere with ABO/Rh typing studies. Several methods to successfully mitigate interference have been described, such as treatment of reagent RBCs with reducing agents or enzymes, allogeneic RBC adsorption studies and drug specific neutralisation assays; all methods have limitations. TSLs should select an approach that best fits their workflow and expertise and takes into consideration their level of access to specialised outside testing, local blood supplier capabilities, and the type of patient population served. For platelet refractory patients, samples should be tested by platelet antibody assays that are known to be unaffected by drug therapy. RBC transfusion support for multiple myeloma patients receiving anti-CD38 or anti-CD47 drugs can be optimised by establishing good communication between the clinical teams and TSLs, building electronic notification processes, and ensuring timely completion of baseline pre-transfusion testing and RBC phenotype/genotype prior to starting therapy. Staff education, standardisation of laboratory mitigation measures, and implementation of testing algorithms that consider mAb-induced interference when working up a pan-agglutinin help to significantly decrease delays that would otherwise result if standard methods were employed to complete antibody identification studies.