Efficacy and safety of cyclosporine A treatment in autoimmune cytopenias: the experience of two Italian reference centers

Abstract

Background: Immune thrombocytopenia (ITP) and autoimmune hemolytic anemia (AIHA) show good responses to frontline steroids. About two-third of cases relapse and require second-line treatment, including rituximab, mainly effective in AIHA, and thrombopoietin-receptor agonists (TPO-RAs) in ITP, while the use of splenectomy progressively decreased due to concerns for infectious/thrombotic complications. For those failing second line, immunosuppressants may be considered. Objectives: The aim of this study was to evaluate the efficacy of cyclosporine treatment in patients with ITP and AIHA. Design: In this retrospective study, we evaluated the efficacy and safety of cyclosporine A (CyA) in ITP ( N = 29) and AIHA ( N = 10) patients followed at two reference centers in Milan, Italy. Methods: Responses were classified as partial [Hb > 10 or at least 2 g/dl increase from baseline, platelets (PLT) > 30 × 109/l with at least doubling from baseline] and complete (Hb > 12 g/dl or PLT > 100 × 109/l) and evaluated at 3, 6, and 12 months. Treatment emergent adverse events were also registered. Results: The median time from diagnosis to CyA was 35 months (3–293), and patients had required a median of 4 (1–8) previous therapy lines. Median duration of CyA was 28 (2–140) months and responses were achieved in 86% of ITP and 50% of AIHA subjects. Responders could reduce or discontinue concomitant treatment and resolved PLT fluctuations on TPO-RA. CyA was generally well tolerated, and only two serious infectious complications in elderly patients on concomitant steroids suggesting caution in this patient population. Conclusion: CyA may be advisable in ITP, which is not well controlled under TPO-RA, and in AIHA failing rituximab, particularly if ineligible in clinical trial.

Molecular pharmacology in complement‐mediated hemolytic disorders

“…The risk of severe infection and thrombosis should be known and prevented. 70 For patients, refractory to or relapsing after rituximab, and not candidates for splenectomy, few options exist, including cytotoxic immunosuppressants, 49,62,65,71 with limited efficacy and several toxicities. Additionally, bone marrow (BM) compensatory response, an important determinant of clinical severity, may be inadequate and patients may benefit from recombinant erythropoietin administration.…”

The choice of new treatments in autoimmune hemolytic anemia: how to pick from the basket?

“…However, there are no published data to support repeated use of rituximab in wAIHA patients who have received this monoclonal antibody and subsequently relapsed. Third-line therapies include unspecific immune suppressants, such as azathioprine, cyclosporine, mycophenolate, and others ( 1 , 57 ). Splenectomy, which was previously often recommended in the second line, is now considered an option in the third or subsequent lines ( 1 , 2 , 14 , 58 ).…”

Rituximab resistance in ITP and beyond

“…Cyclosporin is an immunosuppressant that inhibits the phosphatase activity of calcineurin regulating gene expression in activated T cells and blocking signaling pathways triggered by antigen recognition (137). Cyclosporin was used sporadically prerituximab era as second-line therapy after failure of steroids and splenectomy, with evidence level limited to case reports, retrospective case series and one small prospective study (138)(139)(140)(141)(142)(143). The ORR ranged from 55% to 100% with majority of responses sustained.…”