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All-Trans Retinoic Acid with Low-Dose Rituximab for ITP?
Standard first-line treatment for immune thrombocytopenia (ITP) includes steroids with or without intravenous immune globulins. However, many patients require second line treatment owing to lack of response, intolerance, or relapse. Many second-line options exist, including rituximab, splenectomy, and thrombopoietin agonists. Some investigators have proposed that combining therapies with complementary mechanisms of action might improve response to the second-line options. A prior study showed efficacy from adding all-trans retinoic acid (ATRA), which can induce megakaryocyte differentiation, to danazol in patients with ITP (Lancet Haematol 2017; 4:e487).
Now, investigators report a randomized, multicenter study comparing ATRA plus low-dose rituximab versus low-dose rituximab alone in 168 patients with ITP and lack of sustained response to steroids. The primary endpoint was the rate of overall response, defined as platelet count ≥30 x 109/L on two occasions, with doubling of the platelet count and absent bleeding complications within one year.
The overall response was higher in the combination-therapy group compared to the monotherapy group (80% vs. 59%). Complete response was also higher in the combination group (40% vs. 25%) and relapse was less frequent (48% vs. 79%). The median time to response was the same in both groups (28 days). Adverse events attributed to ATRA included dry skin (40%) and headache/dizziness (19%).
This study demonstrates improved platelet responses with the addition of ATRA to rituximab in patients with ITP needing second-line therapy. Although overall and complete responses were more likely with the addition of ATRA, there was no shortening of the time to response. This study introduces another potential use for ATRA, which revolutionized care for patients with acute promyelocytic leukemia. Treatment options continue to expand for patients with ITP, and a non-immunosuppressive option would be welcomed. Interestingly, the authors suggest a novel future combination of ATRA with thrombopoietin agonists, given their potentially synergistic mechanisms of action.
Wu Y-J et al.
Title: All-trans retinoic acid plus low-dose rituximab vs low-dose rituximab in corticosteroid-resistant or relapsed ITP.
Source: Blood 2022 Jan 20; [e-pub]. (Abstract/FREE Full Text)