Quality Improvement Initiatives to Improve Transfusion Safety and Efficiency for Patients Receiving Daratumumab

Introduction: Daratumumab is an IgG1k monoclonal antibody directed against CD38, a surface glycoprotein expressed on several cell types including erythrocytes and B lymphocytes at various stages in development, including bone marrow precursors and plasma cells. It was initially approved by the FDA in 2015 for the treatment of multiple myeloma and has since garnered additional approvals in other settings leading to a growing number of patients receiving daratumumab. Its anti-B lymphocyte properties are therapeutic in myeloma patients; however, it also binds CD38 on erythrocytes and circulates for up to six months after a dose. This creates a long-term problem when caring for these patients regarding transfusion needs and resources. In particular, daratumumab causes antibody screens to be panreactive, potentially masking the presence of clinically relevant antibodies. Mitigation of this effect requires specialized treatment with dithiothreitol (DTT)-treated reagent erythrocytes to release CD38 from the cell membrane. This step allows for more accurate detection of clinically relevant antibodies, with the noted exception of the Kell system as these antigens are also removed.

Methods: When daratumumab was placed on formulary, we started weekly communication between the laboratory and clinical teams in order to establish best institutional practices. Additionally, a list of patients on daratumumab was created in order to track them across the institution and measure the impact of interventions on their care. These have prompted multiple interventions to improve the safety and efficiency of patients on daratumumab receiving transfusions.

Results: As of January 2018, our laboratory began implementing in-house DTT testing and eliminated the need to send patient samples to a reference laboratory. Beginning in January 2019, DTT-antibody screens (ABSC) were captured in the electronic medical record (EMR). Over the next six months, 173 distinct DTT-ABSC were performed on 41 patients. Of these, 13 received at least one RBC transfusion for a total of 41 units, with 12 (29%) occurring as an outpatient and 29 (71%) as an inpatient. Importantly, all of these transfusions were on the same-day of the DTT-ABSC, reducing the burden of time and cost associated with travel, as well as the morbidities of delayed transfusion. This is a major step forward in patient care as there were previously no "same-day" transfusions when DTT-ABSC was sent to a reference laboratory. The previous reference laboratory turnaround time averaged 1165 minutes compared with 186 minutes for the in-house testing. These initiatives have also resulted in educational efforts, such as the creation of a daratumumab-specific transfusion consent form to be signed by the attending hematologist at the time of starting therapy, outlining the challenges associated with identifying blood for transfusion and documenting that the benefits of transfusion outweigh the potential risks. This form is valid indefinitely and has subverted previous clinical scenarios where inpatients on daratumumab required urgent/emergent transfusion without an in-house hematologist available to consent for the transfusion. Because DTT also eliminates Kell antigens, clinically relevant antibodies may go undetected in samples treated with DTT. Thus, it is our policy to use Kell-negative products for patients who are on daratumumab, unless the patient expresses the Kell antigen.

Conclusions/Future Directions: Daratumumab therapy is becoming increasingly common in hematology practice. Awareness of the laboratory and clinical challenges that accompany its use and working to mitigate them will lead to safer and more timely patient care. In particular, in-house DTT-ABSC has led to same-day results and transfusion on the same outpatient visit. Next steps include additional educational efforts at an institutional level, establishing simple algorithms within the EMR linked with the order for daratumumab (e.g., automatic ABSC prior to administration), and refining our tracking system to better assess future interventions.