Detection of unexpected antibodies in Korean multiple myeloma patients on daratumumab using dithiothreitol‐treated reagent cells is more efficient than extended phenotyping and genotyping

To the Editor, Recently, Tauscher et al. reported that the number of patients with multiple myeloma (MM) on daratumumab forming subsequent red blood cell (RBC) alloantibodies was not as great as expected. According to this study, out of the 244 patients with MM, only four (4/244, 1.6%) exhibited newly formed RBC alloantibodies. Also, the incidence and prevalence of RBC alloimmunization were lower than random patients (2.9%) or patients with other hematologic diseases (2.8%). Additionally, only 145 (145/244, 59.4%) patients received RBC transfusion during daratumumab therapy. In this context, they asserted that baseline phenotyping or genotyping of MM patients on daratumumab, which was recently recommended by the Association for the Advancement of Blood & Biotherapies (AABB), is neither beneficial nor necessary. We want to extend this idea by sharing our experience of practicing a simplified pre-transfusion workup for detection of clinically significant alloantibodies in MM patients on anti-CD38 antibody. In our laboratory, when a blood unit is requested from a patient with MM on daratumumab, we perform antibody screening with dithiothreitol (DTT)-treated reagent RBCs and skip identification or crossmatching if the screening is negative. This workflow is possible because the K antigen has not been reported in the Korean population. On the contrary, identification of anti-K antibodies is important in Western countries because the K antigen has been reported in approximately 9.0% of the Caucasians and African Americans. In addition to CD38, several other antigens are destroyed by DTT, including clinically important antigen as the K or the Dombrock antigens. We retrospectively investigated the rate of alloantibody formation in patients with MM receiving daratumumab. A list of 109 patients with MM on daratumumab (including one patient on isatuximab) was obtained from the electronic medical records from April 2019 to August 2022. The specimens had been antibody-screened on automated analyzers—Galileo NEO (Immucor Gamma, Norcross, GA, USA) or QWALYS-3 (Diagast, Loos, France)—and positive samples from the initial screening were manually retested with the LISS/Coombs gel assay using ID-DiaCell I, II (Bio-Rad, Cressier-sur-Morat, Switzerland). Patient information for MM on daratumumab is obtained at this step, so such samples are screened with DTT-treated reagent RBCs. Specifically, patients' RBCs were mixed with 0.2 M DTT solution, incubated for 30 min at 37°C, and then the agglutination strength was observed on the gel card. RBCs with E antigen and K antigen were used for positive and negative controls, respectively. Episodes of acute and/or delayed hemolytic transfusion reactions were also collected from the Samsung Medical Center (SMC) hemovigilance system. This study was approved by the Institutional Review Board (IRB no. 2022-06-054) of SMC. Among 109 patients, antibody screening by indirect antiglobulin test (IAT) method was positive in 85 (78.0%) patients, and negative in 22 (20.2%) patients. When the 85 positive screening serum samples were tested with DTT-treated reagent RBCs according to the laboratory protocol, only one patient (1/109, 0.9%) with anti-S antibody showed a positive result on following antibody identification. Seventy patients (70/109, 64.2%) received RBC transfusion after initial daratumumab, and all of these patients were followed for potential alloantibodies. For each patient, the sample was collected every 72 h for a new antibody screening test. Also, no apparent acute and/or delayed hemolytic transfusion reaction was observed by the hemovigilance system of our institution (Table 1). Cushing et al. compared the cost of selective testing and universal genotyping on MM patients on daratumumab. According to their study, routine phenotyping or genotyping cost $934.83 when conventional DTT notification method cost $535.76 per patient. Therefore, the daratumumab-associated difference was low in terms of RBC alloimmunization risk. Selective genotyping and provision of phenotypically-matched RBCs were preferred only for patients with clinically significant antibodies. Received: 12 July 2022 Revised: 26 September 2022 Accepted: 27 September 2022