Intravenous Immunoglobulin May Benefit Severe Autoimmune Hemolytic Anemia

Marc Michel

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Off-label use of intravenous immunoglobulin (IVIg), added to the standard of care, provided some benefit in managing severe adult autoimmune hemolytic anemia (AIHA), according to new research.¹

Key findings from the retrospective, observational study revealed the overall response rate (ORR) was 32.4% one week after IVIg treatment in adults with severe and/or transfusion-dependent AIHA.

“In the absence of any clear predicting factor of response and taking into account the cost and the recurrent problems of IVIg shortage, the use of IVIg in this setting should be limited and well weighed,” wrote the investigative team, led by Marc Michel, department of internal medicine and clinical immunology, Henri-Mondor University Hospital, the University of Paris.

A rare, often life-threatening, acquired autoimmune disease, adult AIHA occurs when autoantibodies directed toward antigens of autologous red blood cell membrane lead to accelerated destruction.² Adults admitted to the intensive care unit with severe AIHA experienced a short-term mortality rate of 13% and of 30% after 1 year of follow-up.

In severe cases, the off-label use of IVIg is often considered, given the analogy with immune thrombocytopenia and other autoantibody-mediated autoimmune diseases.³ Due to its pathophysiology, AIHA may be a good candidate for IVIg use, but there is little evidence supporting its efficacy.

This observational, multicenter retrospective study took place from 2013 to 2021, to assess the efficacy and safety of IVIg as a ‘rescue’ therapy for managing adult AIHA. Most patients were identified from the CARMEN-FRANCE AIHA registry—patients were ≥18 years old, had a diagnosis of AIHA defined as hemoglobin level <12 g/dL, with ≥2 features of hemolysis, and ≥1 course of IVIg for managing AIHA.

The primary endpoint was the ORR to IVIg on Day 7. A “response” was defined as an increase of the hemoglobin level ≥2 g/dL on day 7, compared with baseline. A good response was thus a hemoglobin level ≥10 g/dL on day 7, with a ≥2g increase from baseline. Non-responders demonstrated a hemoglobin increase of <2 g/dL or were transfused within 7 days after IVIg.

Among the 78 patients initially screened, 34 patients from 14 centers fulfilled the eligibility criteria. These patients received a median of 1 previous treatment before IVIg and up to 5 at the end of follow-up. A total of 21 patients (62%) were transfused ≥1 time before IVIg administration.

Upon analysis, 11 patients (32.4%) responded to IVIg on day 7, including two with a “good response” and nine with a “response”, while 13 (38.3%) were transfused before day 7 and were considered “non-responders.” On day 14 after administration, the ORR was 57%.

Multivariate analysis revealed the early administration of IVIg after AIHA onset was significantly associated with a higher response rate to IVIg (ORR, 14.571 [95% CI, 1.866 – 338.736]; P = .030).

Safety remained consistent, with no observation of AIHA exacerbation due to IVIg-induced hemolysis. Investigators identified a single case of a thromboembolic event that occurred 5 days after IVIg administration in a 60-year-old man, with a good outcome.

Michel and colleagues noted, to the best of their knowledge, this is the largest study focused on IVIg administration in anemia since more than 30 years ago. However, they indicated limitations of the analysis, including the retrospective design and a low number of patients, could reduce these takeaways.

“In conclusion, based on this retrospective observational study, we confirm that in addition to standard of care, the off-label use of IVIg may be helpful in one-third of adults managed for severe AIHA,” they wrote.

References

1. _{Michel M, Saïr M, Rivière E, et al. Intravenous immunoglobulin as a rescue therapy for severe adult autoimmune hemolytic anemia: Results from a French multicenter observational study. Am J Hematol. Published online May 14, 2024. doi:10.1002/ajh.27361}
2. _{Fattizzo B, Zaninoni A, Nesa F, et al. Lessons from very severe, refractory, and fatal primary autoimmune hemolytic anemias. Am J Hematol. 2015;90(8):E149-E151. doi:10.1002/ajh.24047}
3. _{Jäger U, Barcellini W, Broome CM, et al. Diagnosis and treatment of autoimmune hemolytic anemia in adults: Recommendations from the First International Consensus Meeting. Blood Rev. 2020;41:100648. doi:10.1016/j.blre.2019.100648}