Immunotherapy as rescue for cardiomyopathy in Omenn syndrome

Q: What is the clinical evidence from this study?

Study design: Case Report. Population: Omenn syndrome with severe hypertrophic infiltrative cardiomyopathy (n=1). Intervention: Multimodal immunosuppression with ruxolitinib, mepolizumab, and alemtuzumab. Primary outcome: Resolution of ventricular obstruction, regression of biventricular hypertrophy, and successful bridge to hematopoietic stem cell transplantation.

Q: What does this research mean for the field?

Multimodal immunosuppression targeting eosinophils and lymphocytes (including mepolizumab and alemtuzumab) resolves life-threatening infiltrative cardiomyopathy in Omenn syndrome, enabling successful hematopoietic stem cell transplantation. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

Simon Boutinaud; Vincent Barlogis; Lionel Berthomieu; Montserrat Sierra‐Colomina; Marlène Pasquet

doi:10.70962/jhi.20250046

May 31, 2025Journal of Human ImmunityOpen Access

Immunotherapy as rescue for cardiomyopathy in Omenn syndrome

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Why the study?

Does multimodal targeted immunosuppression with ruxolitinib, mepolizumab, and alemtuzumab improve severe infiltrative hypertrophic cardiomyopathy and enable safe hematopoietic stem cell transplantation in an infant with Omenn syndrome?

Key Points

To report the targeted immunosuppressive rescue of life-threatening infiltrative hypertrophic cardiomyopathy in an infant with Omenn syndrome prior to hematopoietic stem cell transplantation.
Evaluated a 6-month-old infant presenting with erythroderma, eosinophilia, and severe biventricular hypertrophic cardiomyopathy with intra-left ventricular obstruction, genetically confirmed with a homozygous RAG2 mutation.
Administered multimodal immunosuppression consisting of ruxolitinib (5 mg every 12 h), mepolizumab (one 20 mg dose), and alemtuzumab (0.5 mg/kg on day 51, 1 mg/kg on days 52–53) before reduced-intensity conditioning HSCT on day 108.
Treatment produced complete lymphocytic depletion and resolution of hypereosinophilia by day 52, with repeated echocardiogram on day 56 demonstrating complete disappearance of ventricular obstruction.
The infant successfully underwent HLA-matched unrelated donor HSCT without cardiac failure; echocardiograms at 3, 6, and 12 months were normal, and the patient remained asymptomatic at 13 months of follow-up.

Study Design

Type

Case Report (n=1)

Multicenter

No

Structured PICO

Does multimodal targeted immunosuppression with ruxolitinib, mepolizumab, and alemtuzumab improve severe infiltrative hypertrophic cardiomyopathy and enable safe hematopoietic stem cell transplantation in an infant with Omenn syndrome?

P

Population

1 infant (6 months old) with Omenn syndrome and severe corticosteroid-refractory hypertrophic infiltrative cardiomyopathy followed for 13 months after hematopoietic stem cell transplantation.

I

Intervention

Multimodal immunosuppression consisting of oral ruxolitinib 5 mg every 12 hours (days 44 to 88), a single dose of mepolizumab 20 mg (anti-IL-5 monoclonal antibody on day 46), and daily IV alemtuzumab (anti-CD52 monoclonal antibody) from day 51 to 53 (0.5 mg/kg on day 51, 1 mg/kg on days 52-53), as a bridge to HLA-matched unrelated donor hematopoietic stem cell transplantation (HSCT) on day 108.

O

Outcome

Clinical and echocardiographic regression of severe biventricular hypertrophy and intra-left ventricular obstruction, allowing successful bridge to curative hematopoietic stem cell transplantation (followed up to 13 months post-HSCT).hard clinical

Targeted multimodal immunosuppression with mepolizumab and alemtuzumab can rapidly reverse life-threatening infiltrative hypertrophic cardiomyopathy in Omenn syndrome, serving as a safe bridge to curative hematopoietic stem cell transplantation.

Limitations

Single patient case report
Trans-jugular myocardial biopsy was too risky, preventing definitive histopathological confirmation of eosinophilic versus lymphocytic origin
Definitive contribution of ruxolitinib could not be assessed due to the short duration of monotherapy
Single case report design
Lack of histopathological confirmation of the cardiomyopathy etiology because trans-jugular endomyocardial biopsy was considered too risky
Inability to assess the definitive individual contribution of ruxolitinib due to the short duration of monotherapy prior to adding monoclonal antibodies

Implication

Hypothesis-generating for targeted immunosuppression in Omenn syndrome cardiomyopathy; prospective trials needed before clinical adoption.

Abstract

A 6-month-old infant with Omenn syndrome and severe hypertrophic cardiomyopathy showed significant clinical improvement following multimodal immunosuppression with anti-IL-5 and alemtuzumab. This targeted approach successfully stabilized the patient, providing a critical bridge to curative hematopoietic stem cell transplantation.

Discussion

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Cite This Study

Boutinaud et al. (2025) conducted a case report in Omenn syndrome with severe hypertrophic infiltrative cardiomyopathy (n=1). Multimodal immunosuppression with ruxolitinib, mepolizumab, and alemtuzumab was evaluated on Resolution of ventricular obstruction, regression of biventricular hypertrophy, and successful bridge to hematopoietic stem cell transplantation.

synapsesocial.com/papers/6a7926e902ab7a73dd022db6 https://doi.org/10.70962/jhi.20250046

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Immunotherapy as rescue for cardiomyopathy in Omenn syndrome

Figures

Key Points

Study Design

Structured PICO

Limitations

Implication

Abstract

Discussion

Cite This Study

Immunotherapy as rescue for cardiomyopathy in Omenn syndrome

Figures

Key Points

Study Design

Structured PICO

Limitations

Implication

Abstract

Discussion

Cite This Study

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