Considerations for pre‐transfusion immunohaematology testing in patients receiving the anti‐CD38 monoclonal antibody daratumumab for the treatment of multiple myeloma

Abstract

In recent years, the anti-CD38 monoclonal antibody daratumumab (Darzalex; JanssenCilag Pty Ltd) has been shown to be highly efficacious in relapsed and refractory multiple myeloma, with the final results of treatment in newly diagnosed patients awaited. Despite awareness of the potential interference of daratumumab in pre-transfusion immunohaematology testing during phase I and II clinical studies, there was a degree of unpreparedness in the community upon the introduction of this drug into the clinics, particularly the impact that it has on the operational processes in hospital transfusion laboratories and timely issue of red blood cells (RBCs). Anti-CD38 interference in pre-transfusion immunohaematology tests is a particular problem in patients being treated with daratumumab for multiple myeloma as many will require RBC transfusions during their disease treatment. Panagglutination caused by anti-CD38 monoclonal antibody during the indirect antiglobulin test may mask the presence of a clinically significant RBC alloantibody in the patient's plasma during the antibody screen and identification process, which may be overlooked, particularly in urgent situations, subsequently resulting in a delayed or acute haemolytic transfusion reaction. Here, we summarise daratumumab's effects on pre-transfusion immunohaematology testing and its impact on clinical practice and make practical recommendations based on a consensus from medical and scientific transfusion experts and myeloma specialists on behalf of the Australian and New Zealand Society of Blood Transfusion and Myeloma Scientific Advisory Group to Myeloma Australia, respectively.

Risk of RBC alloimmunization in multiple myeloma patients treated by Daratumumab

“…Currently, there is no consensus regarding pre‐transfusion testing for patients being treated with DARA. Two similar algorithms have been published recently . Both recommended transfusion of uncrossmatched O or ABO compatible RBCs when patients needed emergent transfusion.…”

“…Currently, there is no consensus regarding pre-transfusion testing for patients being treated with DARA. Two similar algorithms have been published recently [12,25] [12].…”

The impact of Daratumumab on transfusion service costs

“…Because a basic ABSC is required for all patients per AABB standards, the cost of an ABSC was not included as an additional cost related to DARA interference. The GPSR approach requires an IAT XM for all RBC transfusions since alloantibodies have not been ruled out . Therefore, the cost of an IAT XM for all transfusions versus an EXM for the NATTA patients without RBC antibodies is included in the cost comparison.…”

“…The GPSR approach requires an IAT XM for all RBC transfusions since alloantibodies have not been ruled out. 16 Therefore, the cost of an IAT XM for all transfusions versus an EXM for the NATTA patients without RBC antibodies is included in the cost comparison. The IAT XMs for patients with alloantibodies are not included in the cost comparison because an IAT XM is performed for both approaches.…”

“…[13][14][15] 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. 16 Finally, anti-CD38 idiotype antibodies, soluble CD38 10 , cord blood cell antibody panels, 17 and F(ab 0 ) 2 fragments 18 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.…”