Papain‐treated panels are a simple method for the identification of alloantibodies in multiple myeloma patients treated with anti‐CD38‐based therapies

Carreño‐Tarragona, Gonzalo; Cedena, Teresa; Montejano, Laura; Alonso, Rafael; Mirás, Fatima; Valeri, Antonio; Rivero, Ana; Jj, Lahuerta; Martínez‐López, Joaquín

doi:10.1111/tme.12508

Cited by 15 publications

(11 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Studies in the available literature report favourable outcomes to transfusion in this cohort of patients where ABO/RH/K matched or extended phenotype matched units have been given, with very few transfusion reactions reported and instances of alloimmunisation reported to be low, once daratumumab therapy has commenced. Published rates of alloimmunisation are between 0% and 3% in this cohort of patients [13][14][15][16][17][18][19][20] (see Table I) and studies report a variety of transfusion approaches, including providing RBCs matched for ABO/Rh/K antigens, which is congruent with current BSH guidance, or routine provision of extended matched RBCs to this cohort of patients.…”

Section: Introductionmentioning

confidence: 54%

See 1 more Smart Citation

Alloimmunisation rate of patients on Daratumumab: A retrospective cohort study of patients in England

Bullock

Foster

Clinkard

2021

Transfusion Medicine

View full text Add to dashboard Cite

Objective: Whilst small-scale studies on rates of alloimmunisation of patients on Daratumumab have been undertaken, no large-scale study has been performed to date on this cohort of patients.Background: Patients with multiple myeloma (MM) who are relapsed or refractory to standard treatment are treated with the anti-CD38 therapeutic monoclonal antibody, Daratumumab. Due to the complexity of pre-transfusion compatibility testing, many MM patients in England are referred to Red Cell Immunohaematology (RCI) laboratories for investigation and provision of Red Blood Cell (RBC) components.Methods: Over a 4-month period, patients due to commence, or currently on anti-CD38 therapy were identified and flagged on the RCI Laboratory Information Management System (LIMS). Data was identified and extracted for further analysis.Interrogation of data was performed independently by two subject matter experts, with discrepancies resolved through further enquiry.Results: Of 734 English MM patients, we report an alloimmunisation rate of 0.4% whilst on an anti-CD38 TMAb. This is in line with other smaller cohort studies. Conclusion:Given the low rate of RBC alloimmunisation, consideration should be given to revising the pre-transfusion testing regimen in this cohort. This may improve testing costs, turn-around times and evidence-based patient care.

show abstract

Section: Introductionmentioning

confidence: 54%

“…This is concordant with other, much smaller cohort group studies. [13][14][15][16][17][18][19][20] The overall rate of alloimmunisation in the cohort, defined as the presence of an antibody to a RBC antigen, either existing or newly-formed once daratumumab therapy had begun, was 4%…”

Section: Conclusion/discussionmentioning

confidence: 99%

Alloimmunisation rate of patients on Daratumumab: A retrospective cohort study of patients in England

Bullock

Foster

Clinkard

2021

Transfusion Medicine

View full text Add to dashboard Cite

show abstract

“…Many methods have been developed to negate DARA interference including destruction of CD38 on reagent RBC by dithiothreitol (DTT) or proteolytic enzymes such as trypsin and papain ; masking CD38 with F(ab')2 fragments of DARA ; using CD38‐negative reagent RBC such as cord RBC ; and neutralizing DARA in patient plasma with anti‐DARA idiotype antibody or recombinant human soluble CD38 . DTT denaturation of CD38 on reagent RBC by disruption of disulphide bonds in its extracellular domain is the most widely adopted method to negate DARA interference worldwide .…”

Section: Introductionmentioning

confidence: 99%

Risk of RBC alloimmunization in multiple myeloma patients treated by Daratumumab

Wolf

Mettman

et al. 2019

Vox Sanguinis

View full text Add to dashboard Cite

Background Daratumumab (DARA) is a human monoclonal antibody for the treatment of multiple myeloma (MM). DARA binds to CD38 on RBCs and interferes with detection of RBC alloantibodies. The objective of this study was to evaluate the risk of RBC alloimmunization in MM patients treated with DARA. Materials and methods A retrospective study of the complete serological profile and transfusion history of 45 MM patients received transfusion and treated with DARA from July 2015 to December 2018 was undertaken. All cases with positive Ab screens were treated with DTT to identify RBC alloantibodies. RBC transfusion history was monitored between the first DARA dose to the last or extending to the first negative Ab screen after the last DARA dose if the Ab screen was ever positive. Forty‐six MM patients received transfusion but not DARA were studied as control group. Results Totally 184 Ab screens were done on 45 patients transfused with ABO‐Rh compatible RBCs, phenotypically matched units or both. None of them showed detectable alloantibodies after DTT treatment. The duration of Ab screening positivity varied markedly, ranging from 25 days to 5 months after the last dose. Two of 46 patients in the control group had preexisting alloantibodies but no new alloantibodies were detected during study period. Conclusions Our results indicate that the risk of forming new RBC alloantibodies after transfusion in MM patients treated with current regimens is very low and no DARA‐associated difference in the alloimmunization risk. No significant difference in alloimmunization is detected between ABO‐Rh compatible and phenotypically matched transfusion.

show abstract

“…Six of 43 (14.0%) patients had a positive autocontrol IAT, and 13/67 (19.4%) had positive DAT. One study performed long-term follow-up DAT on three patients who previously had a positive result, and all became negative ( 17 ). Three studies reported on time to resolution of positive IAT after cessation of therapy; the durations were 2–6 months (range), median 5 months (range 1–9 months), and median 3.4 months (range 2.1–6.3) ( 7 , 15 , 17 ).…”

Section: Clinical Data On Impact Of Anti-cd38 Antibodies On Blood Typmentioning

confidence: 99%

Blood Transfusion Management for Patients Treated With Anti-CD38 Monoclonal Antibodies

et al. 2018

View full text Add to dashboard Cite

Daratumumab has proven to be highly efficacious for relapsed and refractory multiple myeloma (MM) and has recently been approved in the frontline setting for MM patients ineligible for transplantation. In the future, expanded indications are possible for daratumumab and other anti-CD38 monoclonal antibodies in development. For several years, it has been recognized that these therapies interfere with blood bank testing by binding to CD38 on red blood cells and causing panagglutination on the Indirect Antiglobulin Test. This can lead to redundant testing and significant delays in patient care. Given the anticipated increase in utilization of anti-CD38 monoclonal antibodies, as well as the transfusion needs of MM patients, it is critical to understand the nature of this interference with blood bank testing and to optimize clinical and laboratory procedures. In this review, we summarize the pathophysiology of this phenomenon, examine the clinical data reported to date, describe currently available methods to resolve this issue, and lastly provide a guide to clinical management of blood transfusions for patients receiving anti-CD38 monoclonal antibodies.

show abstract

Papain‐treated panels are a simple method for the identification of alloantibodies in multiple myeloma patients treated with anti‐CD38‐based therapies

Abstract: Anti-CD38 MAs produce nonspecific interference in blood bank tests. This interference can be overcome by various methods, including DTT or papain treatment as proposed here. These methods have limitations that can be resolved using phenotyped blood units.

Cited by 15 publications

References 11 publications

Alloimmunisation rate of patients on Daratumumab: A retrospective cohort study of patients in England

Alloimmunisation rate of patients on Daratumumab: A retrospective cohort study of patients in England

Risk of RBC alloimmunization in multiple myeloma patients treated by Daratumumab

Blood Transfusion Management for Patients Treated With Anti-CD38 Monoclonal Antibodies

Contact Info

Product

Resources

About