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Research has shown that daratumumab, a monoclonal antibody approved to treat multiple myeloma, interferes with routine compatibility testing for blood transfusion.
And this interference can cause delays in providing patients with compatible blood.
Investigators have discovered ways to eliminate or circumvent the interference, but implementing these methods in hospital blood banks may be challenging.
Michael F. Murphy, MD, of John Radcliffe Hospital in Oxford, UK, and his colleagues discussed this issue in a letter to NEJM.
In a phase 1/2 trial of daratumumab, investigators at different study sites observed that the drug consistently interfered with routine blood compatibility testing. This meant that daratumumab-treated patients sometimes experienced delays in receiving blood transfusions.
Investigation revealed that daratumumab in patient plasma directly binds to CD38 on reagent red blood cells used in the blood bank, which causes false-positive antibody screens.
Unfortunately, standard serological methods to eliminate panreactive antibodies did not affect daratumumab’s interference.
However, an investigator-initiated study revealed a dithiothreitol-based method that can eliminate the interference.1
Another method, involving an anti-daratumumab idiotype, also appears effective, though not readily available.2 And a third method is to issue phenotypically or genotypically matched red cell units.3,4
However, establishing these approaches as routine methods in hospital blood banks will be a major challenge, according to Dr Murphy and his colleagues.
The team also said this issue with daratumumab suggests there is a pressing need to investigate whether new drugs interfere with routine blood bank testing.
Investigations should be performed early during drug development. And if interference with compatibility tests is found, it should be brought to the attention of clinicians and blood banks with advice about how to overcome the interference. 
Photo by Daniel Gay
Research has shown that daratumumab, a monoclonal antibody approved to treat multiple myeloma, interferes with routine compatibility testing for blood transfusion.
And this interference can cause delays in providing patients with compatible blood.
Investigators have discovered ways to eliminate or circumvent the interference, but implementing these methods in hospital blood banks may be challenging.
Michael F. Murphy, MD, of John Radcliffe Hospital in Oxford, UK, and his colleagues discussed this issue in a letter to NEJM.
In a phase 1/2 trial of daratumumab, investigators at different study sites observed that the drug consistently interfered with routine blood compatibility testing. This meant that daratumumab-treated patients sometimes experienced delays in receiving blood transfusions.
Investigation revealed that daratumumab in patient plasma directly binds to CD38 on reagent red blood cells used in the blood bank, which causes false-positive antibody screens.
Unfortunately, standard serological methods to eliminate panreactive antibodies did not affect daratumumab’s interference.
However, an investigator-initiated study revealed a dithiothreitol-based method that can eliminate the interference.1
Another method, involving an anti-daratumumab idiotype, also appears effective, though not readily available.2 And a third method is to issue phenotypically or genotypically matched red cell units.3,4
However, establishing these approaches as routine methods in hospital blood banks will be a major challenge, according to Dr Murphy and his colleagues.
The team also said this issue with daratumumab suggests there is a pressing need to investigate whether new drugs interfere with routine blood bank testing.
Investigations should be performed early during drug development. And if interference with compatibility tests is found, it should be brought to the attention of clinicians and blood banks with advice about how to overcome the interference.
Photo by Daniel Gay
Research has shown that daratumumab, a monoclonal antibody approved to treat multiple myeloma, interferes with routine compatibility testing for blood transfusion.
And this interference can cause delays in providing patients with compatible blood.
Investigators have discovered ways to eliminate or circumvent the interference, but implementing these methods in hospital blood banks may be challenging.
Michael F. Murphy, MD, of John Radcliffe Hospital in Oxford, UK, and his colleagues discussed this issue in a letter to NEJM.
In a phase 1/2 trial of daratumumab, investigators at different study sites observed that the drug consistently interfered with routine blood compatibility testing. This meant that daratumumab-treated patients sometimes experienced delays in receiving blood transfusions.
Investigation revealed that daratumumab in patient plasma directly binds to CD38 on reagent red blood cells used in the blood bank, which causes false-positive antibody screens.
Unfortunately, standard serological methods to eliminate panreactive antibodies did not affect daratumumab’s interference.
However, an investigator-initiated study revealed a dithiothreitol-based method that can eliminate the interference.1
Another method, involving an anti-daratumumab idiotype, also appears effective, though not readily available.2 And a third method is to issue phenotypically or genotypically matched red cell units.3,4
However, establishing these approaches as routine methods in hospital blood banks will be a major challenge, according to Dr Murphy and his colleagues.
The team also said this issue with daratumumab suggests there is a pressing need to investigate whether new drugs interfere with routine blood bank testing.
Investigations should be performed early during drug development. And if interference with compatibility tests is found, it should be brought to the attention of clinicians and blood banks with advice about how to overcome the interference.