New Multiple Myeloma Drug Interferes With Routine Testing Prior to a Transfusion

A letter published in The New England Journal of Medicine (NEJM) provides narrative of a clinical interference that has been documented with the much hailed multiple myeloma drug daratumumab. The letter, which has been sponsored by the drug’s developer Janssen, says that daratumumab may interfere with compatibility testing for blood transfusion and cause a delay in when the patient receives compatible blood.

Approved late last year, daratumumab created a splash at the annual meeting of the American Society for Hematology, because it presented hope for patients who had advanced on 3 prior lines of treatment. It is also the first monoclonal antibody to be approved for multiple myeloma.

At the end of the day though, real-world data proves to be the true test. According to the authors of the NEJM letter, staff at a site that was enrolling patients in a phase 1/2 trial observed interference of the drug with routine blood-compatibility testing. This sometimes resulted in delayed blood transfusions for patients who were being treated with daratumumab because the usual laboratory techniques that eliminate interference from panreactive antibodies did not work.

A dithiothreitol (DTT)-based method was finally developed by researchers at Brigham and Women’s Hospital, wherein plasma samples were first incubated with DTT. This reduced the interaction and binding of daratumumab with CD38 on red blood cells by 92%. The method was shown to be generalizable through an international multicenter study. Other practical methods are also being evaluated to eliminate the antibody interference.

The authors of this letter have urged the clinical community to take steps to promote more routine testing of antibody interference at blood banks. This could prove very important with the increasing number of biological agents, especially antibody-based drug candidates that are currently being developed by the pharmaceutical industry.

“We recommend that investigations be performed early during drug development, certainly during phase 1 studies involving healthy volunteers. If interference with compatibility tests is found, we recommend that it be clearly drawn to the attention of clinicians and blood banks with advice about how to overcome the interference,” the authors write.

Reference

Interference of new drugs with compatibility testing for blood transfusion. N Engl J Med. 2016; 375:295-296. doi: 10.1056/NEJMc1515969.