Micro Classroom No. 13 Professor Warburglar: Clinical management of daratumumab

Figure 1.
Dera pre-infusion administration is ^recommended5

Patients are given 20 mg of methylprednisolone or an equivalent dose of intermediate/long-acting corticosteroids after Dara infusion to reduce the risk of
delayed IRR.
Post-infusion medication, including short- and long-acting bronchodilators and inhaled corticosteroids
, should be considered in patients with a history of chronic obstructive pulmonary disease.
After the first four infusions, if the patient does not develop a major IRR, the above post-inhalation drugs
can be discontinued at the discretion of the physician.
In addition, antiviral prophylaxis should be considered to prevent shingles virus ^{reactivation5}
.

Patients with IRR of any severity should immediately discontinue Dara infusion and be given pharmacologic or supportive care
as needed.
After symptoms clear, the decision to continue the infusion depends on the severity of the IRR, and in most cases the infusion of Dara
can be continued.
When re-inducing Dara infusion after IRR is present, the infusion rate needs to be adjusted according to the severity of IRR occurrence (Figure 2)⁵
.

Figure 2.
After the IRR appears, restart the rate adjustment of the infusion of ^Dara5

Dara's interference with blood transfusion and the method of elimination are also practical problems
that may be encountered in clinical practice.
Dara is a humanized monoclonal antibody ^of IgG1κ 7 that binds to CD38 on the surface of red blood cells and interferes with transfusion compatibility testing, most commonly indirect anti-human globulin testing (IAT) such as antibody screening and crossmatching
.
Since Dara binds to CD38 molecules on the surface of red blood cells, accidental antibody agglutination of red blood cells can be caused after the addition of antiglobulin ^reagents6, but the expression of CD38 on the surface of red blood cells is low, and Dara's interference with blood transfusion is controllable
.
First of all, Dara does not interfere with routine ABO and Rh blood grouping
.
Secondly, although CD38 monoclonal antibody can cause slight hemolysis, resulting in a slight decrease in hemoglobin amount, it does not cause severe autologous hemolysis or hemolytic reactions
after allogeneic transfusion.
If urgent transfusion is required, uncrossmatched ABO/RhD-compatible RBC⁵
can be used according to local blood bank practice.

Common methods to eliminate Dara blood transfusion interference include dithiothreonyl a alcohol (DTT) treatment, dimercaptoethanol (2-Me) treatment, and coagulation amine treatment, and the mechanisms, advantages and disadvantages of each treatment method vary (Figure 3)⁵
.
Among them, DTT is the only globally proven method to overcome the compatibility of Vara interference ^transfusion7, which can eliminate false positives of IAT and solve Dara blood transfusion interference
.
Based on drug accessibility and clinical evidence, China's "Expert Consensus on the Interference of CD38 Monoclonal Antibody on Transfusion Compatibility Detection and Its Response Scheme" recommends the clinical use of coagulated amine method for antibody screening or cross-matching test, or the use of commercially available 2-Me application solution or homemade DTT working solution to remove the transfusion ^{interference of} CD38 monoclonal antibody6
.

Figure 3.
Common methods and advantages and disadvantages of eliminating Dara blood transfusion ^{interference5}

For patients treated with Vara with potential transfusion needs, the clinical management process recommended by expert consensus above should be referred to (Figure 4).

Prior to Dara treatment, the clinician takes a blood sample from the patient, sends it to the transfusion department for blood grouping, conducts antibody screening, and takes the patient's specimen.

After treatment with Dara, when blood transfusion is required, inform the transfusion specialist that DTT, dimercaptoethanol, or coagulated amine may be used to eliminate the effect of Dara on transfusion when performing transfusion compatibility ^testing6
.

Figure 4.
Clinical management process for patients treated with darramumab with potential transfusion ^needs6

summary 

Dara IRR occurs mainly on the first infusion, with less than 1%
of patients experiencing a grade 3 or 4 infusion reaction in subsequent infusions.
Treatment with Dara requires prophylactic medication and control of the infusion rate as recommended to better reduce the risk of IRR

Dara can interfere with transfusion compatibility testing
.
Transfusion compatibility testing should be performed before starting Dara therapy; After Dara treatment, the effects of Dara on blood transfusion can be eliminated using DTT, coagulation, or dimercaptoethanol