Contributions
Abstract: PB2095
Type: Publication Only
Background
More than 70% of patients with Immune Primary Thrombocytopenia (ITP) respond to steroids, but 40 to 70% relapse in the first year follow-up. The use of romiplostim in this group is effective, although 9% failure has been described. In recent literature, there are clinical cases and small series describing the potentiating effect of combined treatment with thrombopoietin analogues and immunosuppresive drugs such as steroids, cyclophosphamide and rituximab. We have not found references to the combined use of azathioprine (AZA) and romiplostim (ROM).
Aims
To describe our experience in the combined use of azathioprine and romiplostim as a rescue treatment in patients with acute or newly diagnosed ITP refractory to corticosteroids or corticosteroid-dependence and refractary to maximal doses of romiplostim monotherapy.
Methods
We analyzed patients with newly diagnosed or persistent ITP, with corticosteroid-dependence or refractory to steroids and refractary to romiplostim, both in monotherapy. We have considered refractoriness to steroids not reaching platelets higher than 30x109/L. Corticosteroid-dependece as the need for ongoing or repeated doses administration of corticosteroids for at least 2 months to maintain a platelet count at or above 30 X109/L and/or to avoid bleeding. We considered refractoriness to romiplostim not get platelets greater than 30x109/L with 10mcg/kg/week for at least 3 consecutive weeks. All patients have been diagnosed in a single center with the same physician responsible for the treatment and follow-up. The initial doses of AZA was 100mg/days (2mg/kg/day) and ROM 10mcg/kg/week. Patients have been evaluated every week untill platelets were higher than 30x109/L for to consecutive weeks, after this they were reviewed monthly.
Results
We treated 4 patients (75% female) with a median age at diagnosis of ITP of 53 years old (RIQ, 20-61 years). Treatments received prior to the use of the combination of AZA and ROM were polyspecific immunoglobulins (Ig), steroids (dexamethasone, prednisone) and romiplostim. Responses to steroids and romiplostin in monotherapy were:
• Median dexamethasone cycles (40mg/days x 4 days) was 2.5 (2-4 cycles, IQR). The initial dose of prednisone was 1-2mg/kg/days with a median treatment day of 31.5 days (28-60 days, IQR). The type of response to steroids was PR with corticode-pendence in one patient, 3 patients NR.
• Median time from ITP diagnosis and romiplostim indication was 9.5 weeks (7-48 weeks, IQR). Median platelets count at the start of romiplostim was 6x109/L (2-13x109/L, IQR). The median platelet count achieved at maximal doses of romiplostim for at least 2 consecutive weeks was 10x109/L (3-19x109/L, IQR).
Once established the refractoriness to romiplostim, we manteined ROM 10mcg/kg/week and AZA was iniciated at 100mg/day. The median time from romiplostim indication to the association with azathioprine was 9.8 weeks (5.5 to 15 weeks, IQR). The median time to response after initiation of combination of AZA and ROM was 21 days (15-35 days, IQR). The types of response were:
• One patient did not respond after 60 days of combined treatment.
• 1 patient with RC maintains for 7 months in the absence of active treatment. The combined was necesary during 8 months.
• 2 CRs still undergoing combined dose reduction (current dose romiplostim 2mcg/kg/week and azathioprine 50mg /d). Median platelets from onset of dose reduction 169x109/L (128-176x109/L, IQR). Duration of RC, 7 and 14 months.
Conclusion
The use of azathioprine and romiplostim in combination could be a safe and effective alternative in subjects refractory to steroids or corticosteroid-dependence and thrombopoietin analogs alone. More studies are needed to clarify the mechanism of complementation between the two drugs.
Session topic: 32. Platelets disorders
Keyword(s): Thrombopoietin (TPO), Refractory, ITP
Abstract: PB2095
Type: Publication Only
Background
More than 70% of patients with Immune Primary Thrombocytopenia (ITP) respond to steroids, but 40 to 70% relapse in the first year follow-up. The use of romiplostim in this group is effective, although 9% failure has been described. In recent literature, there are clinical cases and small series describing the potentiating effect of combined treatment with thrombopoietin analogues and immunosuppresive drugs such as steroids, cyclophosphamide and rituximab. We have not found references to the combined use of azathioprine (AZA) and romiplostim (ROM).
Aims
To describe our experience in the combined use of azathioprine and romiplostim as a rescue treatment in patients with acute or newly diagnosed ITP refractory to corticosteroids or corticosteroid-dependence and refractary to maximal doses of romiplostim monotherapy.
Methods
We analyzed patients with newly diagnosed or persistent ITP, with corticosteroid-dependence or refractory to steroids and refractary to romiplostim, both in monotherapy. We have considered refractoriness to steroids not reaching platelets higher than 30x109/L. Corticosteroid-dependece as the need for ongoing or repeated doses administration of corticosteroids for at least 2 months to maintain a platelet count at or above 30 X109/L and/or to avoid bleeding. We considered refractoriness to romiplostim not get platelets greater than 30x109/L with 10mcg/kg/week for at least 3 consecutive weeks. All patients have been diagnosed in a single center with the same physician responsible for the treatment and follow-up. The initial doses of AZA was 100mg/days (2mg/kg/day) and ROM 10mcg/kg/week. Patients have been evaluated every week untill platelets were higher than 30x109/L for to consecutive weeks, after this they were reviewed monthly.
Results
We treated 4 patients (75% female) with a median age at diagnosis of ITP of 53 years old (RIQ, 20-61 years). Treatments received prior to the use of the combination of AZA and ROM were polyspecific immunoglobulins (Ig), steroids (dexamethasone, prednisone) and romiplostim. Responses to steroids and romiplostin in monotherapy were:
• Median dexamethasone cycles (40mg/days x 4 days) was 2.5 (2-4 cycles, IQR). The initial dose of prednisone was 1-2mg/kg/days with a median treatment day of 31.5 days (28-60 days, IQR). The type of response to steroids was PR with corticode-pendence in one patient, 3 patients NR.
• Median time from ITP diagnosis and romiplostim indication was 9.5 weeks (7-48 weeks, IQR). Median platelets count at the start of romiplostim was 6x109/L (2-13x109/L, IQR). The median platelet count achieved at maximal doses of romiplostim for at least 2 consecutive weeks was 10x109/L (3-19x109/L, IQR).
Once established the refractoriness to romiplostim, we manteined ROM 10mcg/kg/week and AZA was iniciated at 100mg/day. The median time from romiplostim indication to the association with azathioprine was 9.8 weeks (5.5 to 15 weeks, IQR). The median time to response after initiation of combination of AZA and ROM was 21 days (15-35 days, IQR). The types of response were:
• One patient did not respond after 60 days of combined treatment.
• 1 patient with RC maintains for 7 months in the absence of active treatment. The combined was necesary during 8 months.
• 2 CRs still undergoing combined dose reduction (current dose romiplostim 2mcg/kg/week and azathioprine 50mg /d). Median platelets from onset of dose reduction 169x109/L (128-176x109/L, IQR). Duration of RC, 7 and 14 months.
Conclusion
The use of azathioprine and romiplostim in combination could be a safe and effective alternative in subjects refractory to steroids or corticosteroid-dependence and thrombopoietin analogs alone. More studies are needed to clarify the mechanism of complementation between the two drugs.
Session topic: 32. Platelets disorders
Keyword(s): Thrombopoietin (TPO), Refractory, ITP