Week 12 Part 2 - Monoclonal Antibody Therapies

Question 1

Daratumumab (Darzalex)

Answer 1

A.k.a. DARA
Anti-CD38, IgG1 subtype
Used to treat relapsed or refractory Multiple Myeloma
CD38 is overexpressed on MM cells
Lower and variable CD38 expression on RBCs

Question 2

Daratumumab Effects on Testing

Answer 2

Interferes with tests based on the IAT
- screen, ID, XM
Does not interfere with ABO/Rh grouping, or any tests performed @ RT, or any tests not requiring IAT
Problematic because MM patients often require transfusion support

Question 3

Daratumumab Effect on IAT-Based Tests

Answer 3

Panagglutination w/ (usually) neg auto control
DAT is usually negative
Persists for up to 6 mo’s post DARA treatment

Question 4

Why does Daratumumab Complicate Pre-Transfusion Testing?

Answer 4

Masks the presence of clinically significant aby’s

Question 5

How to Overcome Daratumumab Interference

Answer 5

Use 0.2M DTT treated reagent cells
DTT disrupts 5 disulphide bonds in the extracellular domain of CD38, preventing DARA binding to CD38

Question 6

What Antigens does DTT Denature?

Answer 6

Kell, Cartwright, Indian, Lutheran, MER2, Dombrock, Diego, Cromer
DTT-treated cells are negative for these antigens
Antibodies against these antigens won’t be detected during an aby screen/ID/XM using DTT-treated cells

Question 7

What to do Before Patient goes on DTT

Answer 7

Clinical history of the patient is crucial
We need to know that a patient will be started on DARA before first treatment
Group and screen (baseline result)
Perform extended phenotyping
- Rh (C, c, E, e), K, Jka, Jkb, Fya, Fyb, S, s
Genotyping when phenotyping isn’t possible

Question 8

How to Test Once Patients is on DTT

Answer 8

Group as normal
Screen using DTT-treated cells

Question 9

How to Test Once Patients is on DTT - If Screen is Negative

Answer 9

IS or electronic XM using ABO/Rh and Kell compatible units
Pheno/Geno -type-matched RBCs where possible

Question 10

How to Test Once Patients is on DTT - If Screen is Positive

Answer 10

ID using DTT-treated panel cells
Select ag neg cells for XM
Provide pheno/geno -type-matched RBCs where possible
XM by IAT using DTT-treated donor cells

Question 11

Dithiothreitol

Answer 11

Used to negate the effect of DARA interference while preserving K antigenicity

Question 12

Daudi Cells

Answer 12

Potential method to overcome DARA
An alternative to dithiothreitol to resolve DARA interference
They are:
- B lymphoblast cell line
- high CD38 expression

Question 13

CAMELLIA

Answer 13

Anti-CD47, IgG4 subtype
In clinical trials for the treatment of haematologic malignancies and solid tumours
CD47 is expressed on all cell types
E.g. CAMELLIA binds CD47 on tumour cells which then binds to Fc receptor on macrophage => destroying tumour cell

Question 14

Mitigating CAMELLIA Interference

Answer 14

Before starting treatment
- serological tests as for DARA
Adsorb patient plasma w/ papain tx’d R1R1, R2R2, and rr cells for ABO grouping and IS XM
Use Gamma-clone anti-IgG in IAT tests