(P-IG-3) "Where's DARA?" - A Medicinal Game of Anti-CD38 Hide And Seek

Background/Case Studies: Knowledge of current patient medications is important in laboratory testing and can be crucial in the ability to provide blood products in a timely manner. There are drugs that can interfere in routine pretransfusion testing such as anti-CD38 daratumumab (Darzalex) or isatuximab (Sarclisa), which bind directly to reagent RBCs. These anti-CD38 may be given alone or in combination with other drugs like proteasome inhibitors or other antineoplastic agents. Two such anti-CD38 combination regimens include pomalidomide (Pomalyst) [POM] or bortezomib (Velcade) [VEL]; note, anti-CD38 is not included on the prescribing information for either POM or VEL. We report reactivity consistent with anti-CD38 therapy in two patients with a drug history of POM or VEL without reported anti-CD38 medication history.


 

 

 



Study

Design/Methods: Two samples, S1 and S2, were received for routine serologic testing.  Testing was performed by standard methods; plasma was tested at the IAT phase against untreated RBCs, RBCs treated with papain, trypsin, or 0.2M DTT and with serological CD38-negative or In(Lu) RBCs.  LISS or PEG (Werfen) enhancement was used for IAT.  For S1 no medication history was initially provided, and for S2 only VEL was reported.

Results/Findings: S1 and S2 plasma reacted weakly (micro+ or 1+) with all RBCs by LISS, PEG, or papain IAT; autocontrol tests and cord RBC samples were negative.  S1 and S2 plasma tested negative by LISS or PEG IAT with trypsin- or DTT-treated RBCs and serological CD38-negative or In(Lu) RBCs, consistent with anti-CD38. Further in-depth investigation with the clinical team and review of medications prescribed to S1 revealed that POM was given; administration of anti-CD38 could not be confirmed by the hospitals for either S1 or S2.

Conclusions: We report pretransfusion testing findings consistent with anti-CD38 therapy in two patients reported to be on POM or VEL with no reported anti-CD38 history.  Patients with a drug history of POM or VEL who have weak plasma IAT reactivity with all panel RBCs and a negative autocontrol should have anti-CD38 therapy taken into consideration, thoroughly investigated serologically, and accurate drug history obtained. Of note, neither Darzalex nor Sarclisa in combination with POM or VEL are FDA approved for treatment of frontline or newly diagnosed diseases; this, and with other potential off-label use of anti-CD38 can further impede pretransfusion testing laboratories in obtaining an accurate medication history.  Several active trials for Pomalyst or Velcade combination therapy with anti-CD38 are listed on clinicaltrials.gov. Laboratories should consider unreported or unappreciated medications as a possible etiology of unexplained serological testing results and the lack of clinical teams reporting accurate medication history to the blood bank may result in delay of blood bank testing or timely provision of blood for transfusion.