Contributions
Abstract: S145
Type: Oral Presentation
Presentation during EHA23: On Friday, June 15, 2018 from 11:45 - 12:00
Location: Room A10
Background
Spleen tyrosine kinase (Syk), a signaling component of Fc receptors, is associated with macrophage destruction of red blood cells (RBCs) in warm antibody autoimmune hemolytic anemia (wAIHA). The Syk inhibitor fostamatinib diminishes antibody-induced anemia in mice (Podolanczuk et al, Blood 2009;113(14):3154-60).
Aims
This Phase 2 study (NCT02612558) assessed the efficacy and safety of fostamatinib in wAIHA.
Methods
Eligible adult patients had primary or secondary wAIHA with more than one prior failed treatment, hemoglobin (Hgb) <10 g/dL, IgG-positive direct antiglobulin test (DAT), haptoglobin <10 mg/dL, and lactate dehydrogenase (LDH) >ULN. Patients received fostamatinib 150 mg BID for up to 24 weeks. In this Simon two-stage design, if ≥4 patients in Stage 1 achieved the primary efficacy endpoint (Hgb >10 g/dL with an increase of ≥2 g/dL from baseline by Week 24 without rescue therapy or RBC transfusion), suggesting a true response rate of greater than 20% (at alpha=0.10), then Stage 2 would begin enrollment. Data as of February 23, 2018, from Stage 1, are presented.
Results
Of 19 patients with post-baseline assessments, 1 (5%) had a history of lymphoproliferative disease, 5 (26%) had prior splenectomy, 12 (63%) had prior steroids, 1 (5%) had prior ESAs, and none had prior rituximab. The median baseline Hgb was 9.1 g/dL (range: 6.8-9.9). The primary endpoint was met: 9 of 17 (53%) patients had a response, including 1 late responder. Response was generally rapid and sustained; 5 of 9 responses were achieved within 4 weeks. The median duration of the first response was 16.6 weeks (range: 0.1 to >30 weeks). Trends for decreasing LDH and reticulocytes and increasing haptoglobin were observed. The most common adverse events were diarrhea and dizziness. Serious adverse events were reported in 3 patients. None were related to fostamatinib. One patient recovered and continued on treatment. Two patients had serious adverse events resulting in fatalities: one with skin necrosis and infection (immunosuppressed due to steroids) and one elderly patient with pneumonia (immunosuppressed due to steroids and prior CLL).
Conclusion
Fostamatinib markedly improved Hgb levels in some patients with wAIHA. Side effects were manageable and consistent with those previously reported with fostamatinib in other conditions. Based on these results, Stage 2 of this study is currently enrolling patients. Long-term follow-up will provide additional efficacy and safety data for fostamatinib in patients with wAIHA.
Session topic: 29. Enzymopathies, membranopathies and other anemias
Keyword(s): Autoimmune hemolytic anemia (AIHA), Red blood cell, Spleen, Tyrosine kinase inhibitor
Abstract: S145
Type: Oral Presentation
Presentation during EHA23: On Friday, June 15, 2018 from 11:45 - 12:00
Location: Room A10
Background
Spleen tyrosine kinase (Syk), a signaling component of Fc receptors, is associated with macrophage destruction of red blood cells (RBCs) in warm antibody autoimmune hemolytic anemia (wAIHA). The Syk inhibitor fostamatinib diminishes antibody-induced anemia in mice (Podolanczuk et al, Blood 2009;113(14):3154-60).
Aims
This Phase 2 study (NCT02612558) assessed the efficacy and safety of fostamatinib in wAIHA.
Methods
Eligible adult patients had primary or secondary wAIHA with more than one prior failed treatment, hemoglobin (Hgb) <10 g/dL, IgG-positive direct antiglobulin test (DAT), haptoglobin <10 mg/dL, and lactate dehydrogenase (LDH) >ULN. Patients received fostamatinib 150 mg BID for up to 24 weeks. In this Simon two-stage design, if ≥4 patients in Stage 1 achieved the primary efficacy endpoint (Hgb >10 g/dL with an increase of ≥2 g/dL from baseline by Week 24 without rescue therapy or RBC transfusion), suggesting a true response rate of greater than 20% (at alpha=0.10), then Stage 2 would begin enrollment. Data as of February 23, 2018, from Stage 1, are presented.
Results
Of 19 patients with post-baseline assessments, 1 (5%) had a history of lymphoproliferative disease, 5 (26%) had prior splenectomy, 12 (63%) had prior steroids, 1 (5%) had prior ESAs, and none had prior rituximab. The median baseline Hgb was 9.1 g/dL (range: 6.8-9.9). The primary endpoint was met: 9 of 17 (53%) patients had a response, including 1 late responder. Response was generally rapid and sustained; 5 of 9 responses were achieved within 4 weeks. The median duration of the first response was 16.6 weeks (range: 0.1 to >30 weeks). Trends for decreasing LDH and reticulocytes and increasing haptoglobin were observed. The most common adverse events were diarrhea and dizziness. Serious adverse events were reported in 3 patients. None were related to fostamatinib. One patient recovered and continued on treatment. Two patients had serious adverse events resulting in fatalities: one with skin necrosis and infection (immunosuppressed due to steroids) and one elderly patient with pneumonia (immunosuppressed due to steroids and prior CLL).
Conclusion
Fostamatinib markedly improved Hgb levels in some patients with wAIHA. Side effects were manageable and consistent with those previously reported with fostamatinib in other conditions. Based on these results, Stage 2 of this study is currently enrolling patients. Long-term follow-up will provide additional efficacy and safety data for fostamatinib in patients with wAIHA.
Session topic: 29. Enzymopathies, membranopathies and other anemias
Keyword(s): Autoimmune hemolytic anemia (AIHA), Red blood cell, Spleen, Tyrosine kinase inhibitor