AN INTERNATIONAL DELPHI CONSENSUS BUILDING APPROACH TO PATIENT ASSESSMENT AND USE OF IMMUNOGLOBULIN TREATMENT FOR SECONDARY IMMUNE DEFICIENCIES IN HEMATOLOGICAL MALIGNANCY
Author(s): ,
Stephen Jolles
Affiliations:
University Hospital of Wales,Cardiff,United Kingdom
,
Mauricette Michallet
Affiliations:
Université Claude Bernard Lyon,Lyon,France
,
Carlo Agostini
Affiliations:
Ca' Foncello Internal Medicine 1st and Center for,Padua Unversity,Padua,Italy
,
Michael Albert
Affiliations:
Pediatric SCT Program,Dr. von Haunersches University Children's Hospital,Muenchen,Germany
,
David Edgar
Affiliations:
St James’s Hospital & Trinity College Dubli,Dublin,Ireland
,
Roberto Ria
Affiliations:
“Aldo Moro” Medical School, University of Padua,Padua,Italy
,
Livio Trentin
Affiliations:
Department of Medicine-DIMED,University of Padua,Padua,Italy
,
Elisabeth Clodi
Affiliations:
Global Medical&Scientific Affairs,Octapharma Pharm. Prod. Ges.m.b.H.,Vienna,Austria
Vincent Lévy
Affiliations:
Hôpitaux Universitaires Paris-Seine-Saint-Denis,Paris,France
EHA Library. Albert M. 06/12/20; 297829; PB1913
Michael Albert
Michael Albert
Contributions
Abstract

Abstract: PB1913

Type: Publication Only

Background
Secondary immune deficiencies (SID) are caused by various mechanisms and are common in patients with hematological malignancies (HM) e.g. chronic lymphocytic leukemia or multiple myeloma. Both the disease and its treatment (e.g. B-cell ablative therapy) contribute to the development of secondary antibody deficiency. Infections remain a major cause of morbidity and mortality in these patients. This underscores the need for early recognition and stratification of risks in order to guide appropriate treatment, including immunoglobulin replacement therapy (IgRT).

Although EMA approved an expanded use of IgRT in SID in 2019, significant differences remain in the approaches to reduce infection burden across Europe, including different strategies for initiation, dosing and discontinuation of IgRT.

Aims
To help harmonize IgRT use.

Methods
A Task Force comprising international experts in Immunology and Hemato-Oncology drafted statements related to six major areas: Definition of infections, Measuring IgG levels, Initiating IgRT, IgRT dosing, SCIg usage and Discontinuing IgRT.Statements were tested through an international Delphi consensus exercise in three rounds via phone interviews with a panel of 32 European SID specialists (hemato-oncologists & immunologists) aiming to develop recommendations on how to diagnose, treat and follow-up patients with antibody deficiency associated with HM.

Panel feedback on the statements from the first Delphi round was used by the Task Force to refine the statements. In Round 2 the level of agreement with each statement was ranked from 1 “totally disagree” to 6 “totally agree”.

Consensus on a statement was considered to be reached when the level of agreement was 5 (“mostly agree”) or higher among ≥70% of the 32 panelists.

Results
Eighteen of 23 statements achieved consensus in Delphi Round 2. Consensus was reached on definition of infection (severe: requiring IV intervention, immediate or prolonged hospitalization or emergency ICU treatment; recurrent: occurring at least 3 times over a 12-months period despite appropriate anti-infective treatment; persistent:  not improving despite appropriate anti-infective treatment). Consensus was also reached on measurement of IgG levels in patients with HM at the beginning of anti-cancer treatment. As well as on initiation of IgRT in patients with HM who have received appropriate anti-infective therapy during or after a single severe infection or during recurrent or persistent infections when IgG levels are <4 g/l or if test immunization has failed. Recommendation for dosing was to use a minimum IgG maintenance dose of 0.4 g/kg bodyweight every 3-4 weeks. It was also agreed that the option of SCIg treatment should be offered to all patients with HM requiring IgRT.

Stopping IgRT should be considered after at least 6 months without infections and if there is evidence of immunological recovery. These patients should be closely monitored and IgRT should be the treatment of choice if hypogammaglobulinemia and severe or persistent infections recur.

In round 3, another 3 statements achieved consensus after being re-evaluated considering feedback from the full panel, while 2 statements did not reach consensus (“IgG measurement at every routine visit” & “IgRT in HM patients with mild antibody deficiency and infections”).

Conclusion
This Delphi consensus exercise among SID specialists in Europe yielded clear recommendations on initiation, dosing, and discontinuation of IgRT for SID in patients with HM while also highlighting differences in both the initiation of IgRT and measurement of IgG levels in special situations.

Session topic: 06. Chronic lymphocytic leukemia and related disorders - Clinical

Keyword(s): Chronic lymphocytic leukemia, Hematological malignancy, Immunodeficiency, Intravenous gamma-globulin

Abstract: PB1913

Type: Publication Only

Background
Secondary immune deficiencies (SID) are caused by various mechanisms and are common in patients with hematological malignancies (HM) e.g. chronic lymphocytic leukemia or multiple myeloma. Both the disease and its treatment (e.g. B-cell ablative therapy) contribute to the development of secondary antibody deficiency. Infections remain a major cause of morbidity and mortality in these patients. This underscores the need for early recognition and stratification of risks in order to guide appropriate treatment, including immunoglobulin replacement therapy (IgRT).

Although EMA approved an expanded use of IgRT in SID in 2019, significant differences remain in the approaches to reduce infection burden across Europe, including different strategies for initiation, dosing and discontinuation of IgRT.

Aims
To help harmonize IgRT use.

Methods
A Task Force comprising international experts in Immunology and Hemato-Oncology drafted statements related to six major areas: Definition of infections, Measuring IgG levels, Initiating IgRT, IgRT dosing, SCIg usage and Discontinuing IgRT.Statements were tested through an international Delphi consensus exercise in three rounds via phone interviews with a panel of 32 European SID specialists (hemato-oncologists & immunologists) aiming to develop recommendations on how to diagnose, treat and follow-up patients with antibody deficiency associated with HM.

Panel feedback on the statements from the first Delphi round was used by the Task Force to refine the statements. In Round 2 the level of agreement with each statement was ranked from 1 “totally disagree” to 6 “totally agree”.

Consensus on a statement was considered to be reached when the level of agreement was 5 (“mostly agree”) or higher among ≥70% of the 32 panelists.

Results
Eighteen of 23 statements achieved consensus in Delphi Round 2. Consensus was reached on definition of infection (severe: requiring IV intervention, immediate or prolonged hospitalization or emergency ICU treatment; recurrent: occurring at least 3 times over a 12-months period despite appropriate anti-infective treatment; persistent:  not improving despite appropriate anti-infective treatment). Consensus was also reached on measurement of IgG levels in patients with HM at the beginning of anti-cancer treatment. As well as on initiation of IgRT in patients with HM who have received appropriate anti-infective therapy during or after a single severe infection or during recurrent or persistent infections when IgG levels are <4 g/l or if test immunization has failed. Recommendation for dosing was to use a minimum IgG maintenance dose of 0.4 g/kg bodyweight every 3-4 weeks. It was also agreed that the option of SCIg treatment should be offered to all patients with HM requiring IgRT.

Stopping IgRT should be considered after at least 6 months without infections and if there is evidence of immunological recovery. These patients should be closely monitored and IgRT should be the treatment of choice if hypogammaglobulinemia and severe or persistent infections recur.

In round 3, another 3 statements achieved consensus after being re-evaluated considering feedback from the full panel, while 2 statements did not reach consensus (“IgG measurement at every routine visit” & “IgRT in HM patients with mild antibody deficiency and infections”).

Conclusion
This Delphi consensus exercise among SID specialists in Europe yielded clear recommendations on initiation, dosing, and discontinuation of IgRT for SID in patients with HM while also highlighting differences in both the initiation of IgRT and measurement of IgG levels in special situations.

Session topic: 06. Chronic lymphocytic leukemia and related disorders - Clinical

Keyword(s): Chronic lymphocytic leukemia, Hematological malignancy, Immunodeficiency, Intravenous gamma-globulin

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