Avoiding Daratumumab Interference with Blood Typing

Background

Daratumumab is an IgG monoclonal antibody that binds CD38 on hematopoietic cells and induces apoptosis. It is FDA approved for upfront treatment of systemic light chain amyloidosis as well as treatment of frontline and relapsed/refractory multiple myeloma. Daratumumab, similar to other CD38 monoclonal antibodies, interferes with blood compatibility testing by causing panagglunination on the Indirect Antiglobulin Test (IAT) leading to false positive results and delays in blood availability for transfusion. This panagglutination can persist up to 6 months after the last Daratumumab infusion. Additionally, attempts to overcome this may mask the presence of a clinically significant antibody resulting in acute or delayed hemolytic transfusion reactions. Several laboratory techniques like RBC genotyping, phenotyping, and the use of Dithiothretol (DTT) treatment of serum are used to overcome this laboratory abnormality. These are either technically time consuming or not widely available in all healthcare institutions. DTT, though readily available, requires prior notification of the blood bank when a patient who is being treated with Daratumumab needs a transfusion. This labor intensive and time consuming process may result in delays in patient care adverse outcomes. By far, the most cost effective way is to obtain blood type and antibody screen (IAT) prior to the initial Daratumumab administration. However, this requires institutional strategy (policy, procedure and pathway) for all potential patients starting anti CD38 monoclonal antibodies in general and daratumumab in particular, to allow timely typing and screening of blood in preparation for future transfusion needs. This quality improvement project was instituted to obtain a type and screen (T&S) prior to patients starting Daratumumab in order to champion high value healthcare which balances clinical benefit with costs and harms with the ultimate goal of improving patient outcomes.

Methods and Results

We retrospectively identified 32 patients who received their first Daratumumab infusion or subcutaneous injection from 11/1/2017 to 5/31/2020 at Community Medical Centers and Community Cancer Institute in Clovis, California and Fresno, California. 13 patients did not have a T&S done within 30 days prior to initiation of Daratumumab, which translates to 40.6%. We conducted manual chart of all patients prior to the intervention and found 6 patients without prior T&S who required transfusions after starting Daratumumab. Each transfusion was regarded as an event regardless of the units of blood received. We calculated the time from T&S order to receipt of transfusion. In total, there were 15 events which amounts to 1,5990 cumulative minute, with the average time to transfusion (TTT) being 1066 minutes. There were also 6 patients with T&S performed prior to Daratumumab initiation who had a total of 22 transfusion events that took 20417 minutes. The average TTT for this group is 928 minutes. The difference in average TTT between patients who had T&S and those that did not have T&S is 138 minutes, which can be clinically significant. We implemented a T&S as part of "Day 0" in our chemotherapy orders in December 2020. 17 patients received their first Daratumumab from January 2021 to January 2022. 15 patients (88%) had T&S performed and 2 patients did not as they were patients from out of network providers.

Conclusion

We are continuing to gather additional data to see if this improvement results in a decrease in average TTT post implementation. This is quality improvement project represents a major step in reducing delays in blood compatibility testing due to Daratumumab. There are no significant changes in resource utilization since patients who need transfusions will require a T&S to be done regardless. Ensuring that a T&S is performed antecedent to the first Daratumumab treatment will reduce delays in obtaining matched blood products for our myeloma patients. This supports timely transfusions to lower adverse outcomes associated with anemia due to chemotherapy and multiple myeloma.

Boulbol:Pfizer: Honoraria; Sanofi: Speakers Bureau. Abdulhaq:Morphosys: Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Jansen: Membership on an entity's Board of Directors or advisory committees; Genentech: Membership on an entity's Board of Directors or advisory committees; Oncopeptide: Speakers Bureau; Alexion: Speakers Bureau. Bukari:Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; NeoGenomics Laboratories, Inc: Research Funding; EUSA Pharma: Honoraria, Membership on an entity's Board of Directors or advisory committees; Seattle Genetics, Inc: Honoraria, Membership on an entity's Board of Directors or advisory committees; SANOFI: Honoraria; HCG-MorphoSys: Honoraria, Membership on an entity's Board of Directors or advisory committees.