Photo Credit: Nemes Laszlo

The following is a summary of “A real-world pharmacovigilance assessment and literature review of lymphoma development in lipodystrophy,” published in the May 2025 issue of Frontiers in Endocrinology by Brown et al. 

Metreleptin was used as leptin replacement therapy alongside diet and lifestyle changes to manage metabolic complications of leptin deficiency in lipodystrophy, while earlier reports linked metreleptin treatment to T-cell lymphomas in patients with acquired generalized lipodystrophy (AGL).  

Researchers conducted a retrospective study to investigate lymphomas in individuals with lipodystrophy and congenital leptin deficiency (CLD) who were either metreleptin-naïve or had received metreleptin at the time of lymphoma diagnosis through pharmacovigilance data and literature review.  

They identified cases by searching PubMed, Embase, and the Cochrane Library from inception until November 22, 2024, and also reviewed 11 years of post-marketing data from the global safety database (GSD) of the metreleptin marketing authorization holder.  

The results showed 16 individuals with 17 lymphomas from 11 published articles and 1 case report from the GSD. Among metreleptin-naïve individuals, 12 lymphomas were identified: 6 T-cell lymphomas in 6 patients with AGL, 3 B-cell lymphomas in 2 patients with familial partial lipodystrophy and 1 with AGL, and 3 Hodgkin lymphomas each in patients with generalized lipodystrophy, juvenile-onset dermatomyositis-associated lipodystrophy, and CLD and 5 lymphomas occurred in 4 metreleptin-treated individuals; 3 had AGL with T-cell lymphomas reported previously,1 metreleptin-treated individual from the GSD had generalized lipodystrophy-associated atypical progeroid syndrome and developed B-cell and brain lymphomas after solid organ transplant and immunosuppressive therapy. All 9 T-cell lymphomas were found in patients with AGL, who frequently had additional autoimmune or inflammatory conditions.  

Investigators concluded that lymphoma development was likely linked to the underlying disease mechanisms causing lipodystrophy rather than the effects of metreleptin, with T-cell immunoproliferative disorders potentially contributing to autoimmune-related syndromes like AGL, highlighting the importance of hematology in understanding these processes. 

Source: frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2025.1582715/full