The publication, sponsored by Octapharma, marks the first pan-European consensus guidance on the use of IgRT in patients with hypogammaglobulinaemia secondary to haematological malignancies and aims to support harmonisation of clinical practice across Europe.
Octapharma has a longstanding commitment to improving the management of patients with secondary immunodeficiencies (SID) and in 2020 launched PRO-SID, a phase III clinical trial investigating primary infection prophylaxis with intravenous immunoglobulin (IVIg) in patients with chronic lymphocytic leukaemia (CLL). These efforts address the need for both robust clinical data and unified guidance on managing infection risk in patients with SID.
Absence of guidance leaves patients at risk
SAD is a common complication in patients with haematological malignancies such as CLL and multiple myeloma (MM). Up to 85% of CLL patients and up to 83% of patients with smouldering MM have low immunoglobulin levels, which leaves patients more susceptible to infections1,2. Infections are the likely cause of death in 22% of patients with MM and up to 50% of patients with CLL3,4. IgRT is effective at reducing the risk of infections in patients with haematological malignancies5.
In 2019, the EMA approved an expanded use of IVIg in patients with SID6. However, detailed European guidelines on the use of IgRT in patients with haematological malignancies and SAD were lacking. Differences in treatment approaches to reduce the infection burden remain significant across Europe, including different strategies for initiation, dosing and discontinuation of IgRT.
Stephen Jolles, lead author of the publication and Professor at the Immunodeficiency Centre for Wales in Cardiff, UK, commented: “Developing consensus guidelines for the use of IgRT in secondary antibody deficiency (SAD) aims to address a major need for treatment recommendations for patients with haematological malignancies and SAD. IgRT can reduce morbidity and mortality in a selected group of these patients and it is important that physicians have consistent guidance on defining this group and managing infection risk.”
A Task Force of eight experts in immunology and haemato-oncology developed statements on key aspects of IgRT, which were reviewed by a panel of 32 European experts. This Delphi consensus exercise developed clear recommendations for SAD due to haematological malignancies such as: measurement of IgG levels at the beginning of anti-cancer treatment; initiation of IgRT in patients 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; initiation of IgRT with a minimum IgG dose of 0.4 g/kg bodyweight every 3-4 weeks or stopping IgRT after at least 6 months without infections and concomitant evidence of immunological recovery. The 21 consensus statements emphasise the importance of IgRT for patients with SAD who experience severe, recurrent or persistent infections and provide guidance on initiation, dosing and discontinuation of IgRT, as well as measurement of IgG levels and the use of subcutaneous immunoglobulin (SCIg) therapy. The publication is available through open access at "Treating Secondary Antibody Deficiency in Patients with Haematological Malignancy: European Expert Consensus".
More information on SID in patients with haematological malignancies, including detailed information on the recent consensus guidelines, can be found at https://www.secondaryimmunodeficiency.com/
Patient recruitment continues for the PRO-SID study
Recruitment for the phase III PRO-SID study (NCT04502030) of IVIg in patients with CLL and SID is underway, in 22 sites across 7 countries. The PRO-SID study is investigating the efficacy and safety of IVIg (Panzyga®) as primary prophylaxis in patients with CLL and SID. Secondary prophylaxis with IVIg is an established approach to reduce the rate of infections in patients with haematological malignancies and SAD, but there is a need for robust data on IVIg as primary infection prophylaxis, i.e. before a major infection occurs7.
Commenting on Octapharma’s involvement in the field of SID, Olaf Walter, Board Member at Octapharma, said that: “Infections remain a serious concern for patients with haematological malignancies and SID, and at Octapharma we continue to strive for a better understanding of how to minimise the risk of such potentially life-threatening complications.”
About the PRO-SID study
The PRO-SID study (NCT04502030) is a prospective, double-blind, randomised, multi-centre, placebo-controlled, interventional, phase III study investigating the efficacy and safety of Panzyga® in patients with chronic lymphocytic leukaemia (CLL) and hypogammaglobulinaemia (IgG < 5 g/L) who are receiving antineoplastic treatment. The study is conducted at multiple sites across Europe (Italy, Poland, Denmark, Hungary, Germany and Russia) and the USA and plans to recruit at least 240 patients.
About Panzyga®
Panzyga® is a 10% human normal immunoglobulin solution ready for intravenous administration. Panzyga® is approved for use in treatment of primary immunodeficiency and idiopathic thrombocytopenic purpura in the USA, Europe and Canada. It is also approved for secondary immunodeficiencies and Guillain Barré syndrome in Europe and Canada and for Kawasaki disease, chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and multifocal motor neuropathy (MMN) in Europe.
About Octapharma
Headquartered in Lachen, Switzerland, Octapharma is one of the largest human protein manufacturers in the world, developing and producing human proteins from human plasma and human cell lines.
Octapharma employs more than 9,000 people worldwide to support the treatment of patients in 118 countries with products across three therapeutic areas: Haematology, Immunotherapy, and Critical Care.
Octapharma has seven R&D sites and six state-of-the-art manufacturing facilities in Austria, France, Germany, Mexico and Sweden, and operates more than 160 plasma donation centres across Europe and the USA.
References
- Patel SY, Carbone J, Jolles S. The Expanding Field of Secondary Antibody Deficiency: Causes, Diagnosis, and Management. Frontiers in Immunology 2019; 10 (DOI: 10.3389/fimmu.2019.00033).
- Kyle RA, Remstein ED, Therneau TM, Dispenzieri A, Kurtin PJ, Hodnefield JM, Larson DR, Plevak MF, Jelinek DF, Fonseca R, Melton LJ, Rajkumar SV. Clinical course and prognosis of smoldering (asymptomatic) multiple myeloma. N Engl J Med 2007; 356:2582-90.
- Blimark C, Holmberg E, Mellqvist UH, Landgren O, Bjorkholm M, Hultcrantz M, Kjellander C, Turesson I, Kristinsson SY. Multiple myeloma and infections. Haematologica 2015; 100:107-13.
- Compagno N, Malipiero G, Cinetto F, Agostini C. Immunoglobulin replacement therapy in secondary hypogammaglobulinemia. Frontiers in Immunology 2014; 5:626.
- Benbrahim O, Viallard J-F, Choquet S, Royer B, Bauduer F, Decaux O, Crave J-C, Fardini Y, Clerson P, Lévy V. The use of octagam and gammanorm in immunodeficiency associated with hematological malignancies: a prospective study from 21 French hematology departments. Hematology 2019; 24:173-82.
- EMA. Guideline on core SmPC for human normal immunoglobulin for intravenous administration (IVIg) 2019; https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-core-smpc-human-normal-immunoglobulin-intravenous-administration-ivig-rev-5_en.pdf
- Agostini C, et al. Prophylactic immunoglobulin therapy in secondary immune deficiency – an expert opinion. Expert Rev Clin Immunol 2016; 12:921-926.