• Plasma reacted weakly (micro to 1+) with all cells in tube LISS IAT with both untreated and papain treated Quotient panel cells• reactivity strength was unchanged between

untreated or papain treated RBCs • Plasma reacted +/- to 2+ in the IgG gel test with all

untreated cells and 1+ to 3+ with papain treated cells in the Bio-Rad panel • Plasma anti-CD38 reactivity was enhanced in 90%

of tests using the Bio-Rad papain panel• No weakening of anti-CD38 reactivity was observed in

any sample using either Bio-Rad or Quotient papain panels

• Notably, isatuximab anti-CD38 plasma reactivity was markedly enhanced with papain treated panel RBCs• +/- untreated vs. 2+ papain treated

Ø Sample Cohort

• 26 previously evaluated samples from patients receiving anti-CD38 therapy were tested• Daratumumab n=25• Isatuximab n=1

Ø Serological Testing

• Samples were tested against untreated and papain treated commercial panels• Quotient • Bio-Rad

• Testing was performed by standard hemagglutination methods:• Quotient panel by tube LISS IAT • Bio-Rad panel by IgG gel test

• The number of patient samples selected aimed to randomly represent various circulating anti-CD38 plasma concentrations and dosing regimens

1. Chapuy et al. Resolving the daratumumab interference with blood or compatibility testing. Transfusion (2015);55;1545-1554

2. Carreño-Tarragona et al. Papain-treated panels are a simple method for the identification of alloantibodies in multiple myeloma patients treated with anti-CD38-based therapies. Transfusion Medicine. 2018

3. Mann, G. A Novel Adjunct automated blood bank method to manage interference from the monoclonal anti-Cd38 drug daratumumab [abstract]. Vox Sanguinis (2017) 112 (Suppl. 1), 195

INTRODUCTION

MATERIALS AND METHODS

RESULTS CONCLUSIONS

REFERENCES

• Anti-CD38 therapy (e.g. Daratumumab, Isatuximab) is used to treat multiple myeloma and other hematological disorders

• Circulating drug in plasma binds to CD38 on RBCs causing interference in blood bank testing

• Strategies to eliminate interference aim to remove or denature CD38 on RBCs by pretreatment with trypsin or 0.2M DTT1

• Previous studies have shown that papain or ficin treatment did not eliminate anti-CD38 interference

• Recent reports (primarily from Europe) indicate that papain treated RBCs may be effective in avoiding anti-CD38 interference • Carreño-Tarragona et al. 2 report that anti-CD38 is

not detected in the IAT using a commercial papain panel and suggest the method is an effective mitigation strategy

• Mann3 advocated the use of papain treated panels with neutral gel cards to test for underlying antibodies that agglutinate at 37C

TESTING SAMPLES FROM PATIENTS RECEIVING ANTI-CD38 THERAPY WITH COMMERCIAL PAPAIN TREATED REAGENT RED CELLS Randall W. Velliquette1, Gayane Shakarian1, Christine Lomas-Francis1 and Connie M. Westhoff11. Immunohematology and Genomics Laboratory, New York Blood Center, New York, NY

The aim of this study was to:• Revaluate the use of papain treated RBCs to

overcome anti-CD38 interference • Test commercial papain panels with a battery of anti-

CD38 patient plasma samples

CD38 on RBCs

• We investigated the possibility that commercialpapain treated RBCs might differ from our experience using in-house treated RBCs

• Anti-CD38 reactivity in IAT was not eliminated in either LISS tube or IgG gel testing

• Reactivity was enhanced with Bio-Rad papain treated RBCs in IgG gel

• The use of papain treated commercial RBCs was NOT effective in eliminating anti-CD38 interference as reactivity remained in the IAT and will interfere with clinically significant antibody detection in the IAT

• Use of papain treated RBCs might enhance underlying 37C reactive Rh antibodies and may be helpful if only 37C reactive antibodies are present2

• Availability of a commercial remedy to avoid anti-CD38 plasma interference would be attractive

OBJECTIVES

I N N O VA T I O N � E X P E R I E N C E � E X P E R T I S E

Blood Center Enterprises

Egea PF 2012, PLOS one 0034918

• 5 disulfide bonds (red arrow) in CD38

• Treatment of RBCs with DTT destroys

structure of CD38

• Trypsin cleaves arginine (R) or lysine (L) in

CD38

• Papain has no denaturing effect on CD38