Contributions
Abstract: S431
Type: Oral Presentation
Presentation during EHA22: On Saturday, June 24, 2017 from 11:30 - 11:45
Location: Room N101
Background
Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by increased platelet destruction and impaired platelet production. Despite decades of basic and clinical research, the treatment of severe, corticosteroid-resistant or relapsed disease remains a great challenge. Our preliminary study indicated the effectiveness of all-trans retinoid acid (ATRA) for ITP (Wang M, et al. ASH 2012, Abstract #3338). This has been coupled with previous discoveries of an immune-modulation effect of ATRA in ITP, including its role to induce changes in Treg cells (Ruan CG 2016), and to correct the imbalance of aberrant macrophage polarization (unpublished data), indicating ATRA as a potential therapeutic regimen. Danazol has been used in the treatment of ITP for more than 30 years. Apart from its haemopoietic stimulatory and immune-modulatory effect, it has recently been shown to reverse abnormal telomere/telomerase function in patients with thrombocytopenia (Townsley DM 2016). The combination of ATRA and danazol may work synergistically based on the mechanism of action targeting both increased platelet destruction and insufficient platelet production.
Aims
To investigate the efficacy and safety of ATRA plus danazol in patients with corticosteroid-resistant and/or relapsed ITP.
Methods
A multicentre prospective study was performed in non-splenectomized corticosteroid resistant/relapsed ITP patients. Participants were at least 18 years of age, had a platelet count of less than 30×109/L at enrolment, and did not achieve a sustained response to treatment with full-dose corticosteroids for a minimum duration of 4 weeks or relapsed during steroid-tapering or after its discontinuation. Written informed consents were obtained from all of the participants. The primary endpoint was a sustained response. The secondary endpoints included overall response, time of response, duration of response, incidence of bleeding symptoms and safety.
Results
From 2012 to 2016, 130 consecutive patients were enrolled from 5 different tertiary medical centres in China. Thirty-seven patients were ineligible and excluded, leaving 93 patients randomized to the ATRA+danazol group (n=45) and the danazol group (n=48). At 12 months’ follow-up, sustained partial or complete response was achieved in 71.6% of patients in the danazol+ATRA group, significantly higher than 47.2% for danazol monotherapy (p<0.001). Additionally, 92.5% and 42.5% of patients receiving ATRA+danazol achieved at least one response (R), while only 58.3% and 11.1% of patients with danazol monotherapy achieved R and CR, respectively. In patients achieving CR or R, the median time to treatment response was 30.5 days with a peak platelet count of 155×109/L in the danazol+ATRA group compared with 49 days with a peak PLT of 69×109/L in the danazol group. Multivariate analysis revealed that the initial response at day 28 and the median ITP duration were the potential variables associated with a sustained response. There was no treatment-related death due to adverse events. One patient receiving danazol monotherapy died from intracranial haemorrhage 4 weeks after study enrollment.
Conclusion
Our findings demonstrate that the combination of ATRA and danazol is safe and effective in achieving a rapid and long-lasting response, making it a potential promising therapeutic option for patients with non-splenectomized corticosteroid-resistant/relapsed ITP. This study is registered at www.clinicaltrials.gov as # NCT01667263.
Session topic: 32. Platelets disorders
Keyword(s): Corticosteroids, ALL-trans retinoic acid (ATRA), Immune thrombocytopenia (ITP)
Abstract: S431
Type: Oral Presentation
Presentation during EHA22: On Saturday, June 24, 2017 from 11:30 - 11:45
Location: Room N101
Background
Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by increased platelet destruction and impaired platelet production. Despite decades of basic and clinical research, the treatment of severe, corticosteroid-resistant or relapsed disease remains a great challenge. Our preliminary study indicated the effectiveness of all-trans retinoid acid (ATRA) for ITP (Wang M, et al. ASH 2012, Abstract #3338). This has been coupled with previous discoveries of an immune-modulation effect of ATRA in ITP, including its role to induce changes in Treg cells (Ruan CG 2016), and to correct the imbalance of aberrant macrophage polarization (unpublished data), indicating ATRA as a potential therapeutic regimen. Danazol has been used in the treatment of ITP for more than 30 years. Apart from its haemopoietic stimulatory and immune-modulatory effect, it has recently been shown to reverse abnormal telomere/telomerase function in patients with thrombocytopenia (Townsley DM 2016). The combination of ATRA and danazol may work synergistically based on the mechanism of action targeting both increased platelet destruction and insufficient platelet production.
Aims
To investigate the efficacy and safety of ATRA plus danazol in patients with corticosteroid-resistant and/or relapsed ITP.
Methods
A multicentre prospective study was performed in non-splenectomized corticosteroid resistant/relapsed ITP patients. Participants were at least 18 years of age, had a platelet count of less than 30×109/L at enrolment, and did not achieve a sustained response to treatment with full-dose corticosteroids for a minimum duration of 4 weeks or relapsed during steroid-tapering or after its discontinuation. Written informed consents were obtained from all of the participants. The primary endpoint was a sustained response. The secondary endpoints included overall response, time of response, duration of response, incidence of bleeding symptoms and safety.
Results
From 2012 to 2016, 130 consecutive patients were enrolled from 5 different tertiary medical centres in China. Thirty-seven patients were ineligible and excluded, leaving 93 patients randomized to the ATRA+danazol group (n=45) and the danazol group (n=48). At 12 months’ follow-up, sustained partial or complete response was achieved in 71.6% of patients in the danazol+ATRA group, significantly higher than 47.2% for danazol monotherapy (p<0.001). Additionally, 92.5% and 42.5% of patients receiving ATRA+danazol achieved at least one response (R), while only 58.3% and 11.1% of patients with danazol monotherapy achieved R and CR, respectively. In patients achieving CR or R, the median time to treatment response was 30.5 days with a peak platelet count of 155×109/L in the danazol+ATRA group compared with 49 days with a peak PLT of 69×109/L in the danazol group. Multivariate analysis revealed that the initial response at day 28 and the median ITP duration were the potential variables associated with a sustained response. There was no treatment-related death due to adverse events. One patient receiving danazol monotherapy died from intracranial haemorrhage 4 weeks after study enrollment.
Conclusion
Our findings demonstrate that the combination of ATRA and danazol is safe and effective in achieving a rapid and long-lasting response, making it a potential promising therapeutic option for patients with non-splenectomized corticosteroid-resistant/relapsed ITP. This study is registered at www.clinicaltrials.gov as # NCT01667263.
Session topic: 32. Platelets disorders
Keyword(s): Corticosteroids, ALL-trans retinoic acid (ATRA), Immune thrombocytopenia (ITP)