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DARATUMUMAB; CHALLENGES OF INTEGRATING THIS NEW THERAPY INTO STANDARD CARE.
Author(s):
Linda Little
,
Linda Little
Affiliations:
Haemato-Oncology,Cancer Centre London, Parkside,London,United Kingdom
Ray Powles
Ray Powles
Affiliations:
Haemato-Oncology,Cancer Centre London, Parkside,London,United Kingdom
(Abstract release date: 05/18/17) EHA Library. Little L. 05/18/17; 182693; PB1979
Linda Little
Linda Little
Contributions
PDF Abstract
Abstract

Abstract: PB1979

Type: Publication Only

Background
Daratumumab (Darzalex) is the first anti-CD38 human Monoclonal Antibody approved for Multiple Myeloma (MM). Targeting the CD38 antigen on the surface of MM cells it causes apoptosis, and has an immune modulated tumour lysis effect. Success in Clinical trials meant that this drug, administered as single agent, or in combination with other novel therapies (Lenalidomide or Bortezomib), received accelerated FDA Approval in the US. It is now being introduced into standard hospital care.

Aims
Daratumumab presents unique challenges to the delivery of risk managed care, due to effects on some blood and bone marrow testing, and to the Infusion Related Reactions (IRRs) seen at the outset of treatment. This poster will highlight important aspects of the treatment pathway for this new therapy, from a single centre perspective.

Methods
We outline the pathways integrated at MDT level; patient characteristics and adverse event profiles of the 15 myeloma patients we have treated with Daratumumab, in a standard service setting.

Results
Daratumumab (Dara) affects certain pathology tests so samples should be clearly identified. Relevant laboratory teams need to be aware of the methods used to process samples. Daratumumab binds to CD38 on Red Blood Cells, and therefore with Cross Match Compatibility testing and Antibody Screening. Obtaining RBC Products for patients receiving Dara will take longer, requiring up to 48 hours’ notice. Cross match samples taken prior to treatment provide the National Blood Service Laboratory with a baseline antigen profile to aid selection of suitable blood products.

Dara is detected during Paraprotein Electrophoresis; Pre and Post baseline samples help to identify the Darzalex Band in the serum; our lab use a Sebia capillarys 2 analyser to separate the Dara band for accurate reporting. Bone Marrow Testing: Daratumumab affects Immunophenotyping by masking the CD38 epitope used to identify plasma cells by flow cytometry; special kits are available using a different CD38 epitope thus dealing with this issue.
Infusion Related Reactions (IRRs) have been reported in over half of patients receiving Daratumumab: 95% of these were seen at the first dose. Typically involving the upper respiratory tract and include rhinitis, cough, wheeze, bronchospasm, laryngospasm and chest pain. More rarely they include rash, fever, and nausea. Reactions can be grade 1 -4 so it’s important that the patient is closely monitored where there is quick access to specialist staff, resuscitation equipment and respiratory support in a high dependency setting. Staff training is important, and patients made aware that they report all new symptoms so the infusion is interrupted immediately and the IRRS treated and re-started at a lower rate when the symptoms have resolved. Premedication is given one hour prior to infusion and patients with a history of COPD receive extra support. Patient characteristics. Total:15
AgeGenderNumber of prior treatmentsRegimensDisease outcome
Range:36-81years
Mean: 61 years
Male: 8
Female: 7
Range: 2-14
Median: 4
Single agent Dara: 1
Dara with Lenalidomide: 4
Dara with Bortezomib: 1
Response: 14
Progression: 1
1st dose datesIRRs LogIRRs seenGradesInfusion duration
27.7.2016-15.11.2016
IRRs: 14/15
(no IRRs 1).
Total completed: 13
Total aborted: 2 (both successfully re-challenged at second dose).
Common: Nasal congestion. Rhinitis. Throat irritation. Cough. bronchospasm. Chest pain. dyspnoea.
Rare:
Rash, nausea. Fever, hypotension.
1-3
Range: 6hr30 - 10hr55.
Mean: 8hr39
1 aborted at 65mins
1 aborted at 10hrs

Conclusion

Education, to include Blood Transfusion, Protein and Histopathology laboratory, and High Dependency Unit staff, in the key aspects of monitoring and risk management are an important part of integrating this new therapy to the treatment pathway for myeloma patients. Daratumumab is likely to become an important treatment for improving both Outcomes and Quality of Life for Myeloma patients going forward.

Session topic: 14. Myeloma and other monoclonal gammopathies - Clinical

Keyword(s): CD38, Cancer immunotherapy

Abstract: PB1979

Type: Publication Only

Background
Daratumumab (Darzalex) is the first anti-CD38 human Monoclonal Antibody approved for Multiple Myeloma (MM). Targeting the CD38 antigen on the surface of MM cells it causes apoptosis, and has an immune modulated tumour lysis effect. Success in Clinical trials meant that this drug, administered as single agent, or in combination with other novel therapies (Lenalidomide or Bortezomib), received accelerated FDA Approval in the US. It is now being introduced into standard hospital care.

Aims
Daratumumab presents unique challenges to the delivery of risk managed care, due to effects on some blood and bone marrow testing, and to the Infusion Related Reactions (IRRs) seen at the outset of treatment. This poster will highlight important aspects of the treatment pathway for this new therapy, from a single centre perspective.

Methods
We outline the pathways integrated at MDT level; patient characteristics and adverse event profiles of the 15 myeloma patients we have treated with Daratumumab, in a standard service setting.

Results
Daratumumab (Dara) affects certain pathology tests so samples should be clearly identified. Relevant laboratory teams need to be aware of the methods used to process samples. Daratumumab binds to CD38 on Red Blood Cells, and therefore with Cross Match Compatibility testing and Antibody Screening. Obtaining RBC Products for patients receiving Dara will take longer, requiring up to 48 hours’ notice. Cross match samples taken prior to treatment provide the National Blood Service Laboratory with a baseline antigen profile to aid selection of suitable blood products.

Dara is detected during Paraprotein Electrophoresis; Pre and Post baseline samples help to identify the Darzalex Band in the serum; our lab use a Sebia capillarys 2 analyser to separate the Dara band for accurate reporting. Bone Marrow Testing: Daratumumab affects Immunophenotyping by masking the CD38 epitope used to identify plasma cells by flow cytometry; special kits are available using a different CD38 epitope thus dealing with this issue.
Infusion Related Reactions (IRRs) have been reported in over half of patients receiving Daratumumab: 95% of these were seen at the first dose. Typically involving the upper respiratory tract and include rhinitis, cough, wheeze, bronchospasm, laryngospasm and chest pain. More rarely they include rash, fever, and nausea. Reactions can be grade 1 -4 so it’s important that the patient is closely monitored where there is quick access to specialist staff, resuscitation equipment and respiratory support in a high dependency setting. Staff training is important, and patients made aware that they report all new symptoms so the infusion is interrupted immediately and the IRRS treated and re-started at a lower rate when the symptoms have resolved. Premedication is given one hour prior to infusion and patients with a history of COPD receive extra support. Patient characteristics. Total:15
AgeGenderNumber of prior treatmentsRegimensDisease outcome
Range:36-81years
Mean: 61 years
Male: 8
Female: 7
Range: 2-14
Median: 4
Single agent Dara: 1
Dara with Lenalidomide: 4
Dara with Bortezomib: 1
Response: 14
Progression: 1
1st dose datesIRRs LogIRRs seenGradesInfusion duration
27.7.2016-15.11.2016
IRRs: 14/15
(no IRRs 1).
Total completed: 13
Total aborted: 2 (both successfully re-challenged at second dose).
Common: Nasal congestion. Rhinitis. Throat irritation. Cough. bronchospasm. Chest pain. dyspnoea.
Rare:
Rash, nausea. Fever, hypotension.
1-3
Range: 6hr30 - 10hr55.
Mean: 8hr39
1 aborted at 65mins
1 aborted at 10hrs

Conclusion

Education, to include Blood Transfusion, Protein and Histopathology laboratory, and High Dependency Unit staff, in the key aspects of monitoring and risk management are an important part of integrating this new therapy to the treatment pathway for myeloma patients. Daratumumab is likely to become an important treatment for improving both Outcomes and Quality of Life for Myeloma patients going forward.

Session topic: 14. Myeloma and other monoclonal gammopathies - Clinical

Keyword(s): CD38, Cancer immunotherapy

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