Treating hematologic immune dysregulation in inborn errors of immunity: a real-life multicenter study.

BACKGROUND

Hematologic immune dysregulation (H-ID) - including autoimmune cytopenia (AIC), lymphoproliferation (LPD), and hemophagocytic lymphohistiocytosis (HLH) - is a potentially life-threatening manifestation of inborn errors of immunity (IEI). Despite the availability of targeted therapies, its management remains challenging, with no standardized treatment strategies established.

OBJECTIVE

To evaluate the efficacy and safety of the available treatments for H-ID, with a specific focus on the treatment indications and outcome differences between targeted versus non-targeted therapies.

METHODS

This multicentric retrospective study included 116 patients with IEI and H-ID across Italian tertiary care centers. Data included treatment indications, response rate, and incidence of adverse events (AEs).

RESULTS

We included patients with autoimmune lymphoproliferative immunodeficiencies (ALPID, 37.1%), humoral immunodeficiencies (31%), syndromic IEI (8.6%), and combined immunodeficiencies (8.6%). H-ID consisted of AIC (67.2%), LPD (71.6%), and HLH (9.5%). 85.3% of patients received treatment, including on-demand therapies (37.9%), long-term treatments (LTT, 84.8%), and hematopoietic stem-cell transplantation (HSCT; 9.1%). LTT included sirolimus (42.9%), mycophenolate mofetil (34.5%), rituximab (29.8%), and targeted therapies (17.9%). Sirolimus showed a higher complete response (CR) rate (61.1%), especially in ALPID patients and those with lymphoproliferation (72%). CR rate was significantly higher in patients receiving targeted therapies (80% vs 43.4%, p < 0.05). AEs were reported in 13.3% of cases, leading to drug withdrawal in 3.6%.

CONCLUSIONS

The indications for LTT and HSCT in H-ID are still heterogeneous. Response rates are variable and influenced by the underlying diagnosis. Targeted therapies are associated with an improved response, the suboptimal molecular diagnosis rate currently limits their use.