According to findings from a phase II SOAR study presented at the 23rd Congress of the European Hematology Association, twice-daily fostamatinib offered short-term improvement in hemoglobin levels among patients with primary or secondary warm antibody autoimmune hemolytic anemia (wAIHA).
“There is no approved treatment for wAIHA other than corticosteroids. Often, prolonged corticosteroid treatment is the only option for patients,” study investigator and presenter David J. Kuter, MD, DPhil, from Massachusetts General Hospital, told ASH Clinical News.
Fostamatinib, an oral spleen tyrosine kinase inhibitor, “reduces red blood cell clearance by macrophages and produces a rapid and significant rise in hemoglobin,” he explained. “This may allow many patients to attain a hemoglobin response and thereby avoid the need for corticosteroids.”
The trial enrolled 19 adult patients with either primary or secondary wAIHA that failed to respond to at least one prior line of therapy. Participants presented with hemoglobin and haptoglobin levels of <10 g/dL and <10 mg/dL, respectively, and all patients had an immunoglobin G-positive direct antiglobulin test and a lactate dehydrogenase (LDH) level greater than the upper limit of normal.
Patients’ most common prior therapies were steroids (n=12; 63%) and erythropoiesis-stimulating agents (n=1; 5%). A lymphoproliferative disease or splenectomy were reported in one (5%) and five (26%) patients, respectively.
At baseline, the median hemoglobin level was 9.1 g/dL (range = 6.8-9.9 g/dL). All patients received fostamatinib 150 mg twice daily for at least 24 weeks. At 24-week follow-up, nine patients (53%) responded to therapy and met the primary efficacy endpoint (hemoglobin >10 g/dL, with ≥2 g/dL increase from baseline without need for a red blood cell transfusion or rescue therapy).
Although one patient responded late to treatment, “response was generally rapid and sustained,” the researchers noted, with five of the nine responses achieved within four weeks.
Among all patients whose disease responded to fostamatinib and who achieved the primary endpoint, the median duration of the initial response was 16.6 weeks (range = 0.1 to >30 weeks). Although the investigators observed lower LDH and reticulocyte levels and higher haptoglobin levels in some patients, none of these associations reached statistical significance.
Three patients reported serious adverse events (AEs), with the most common AEs being diarrhea and dizziness. Although these occurred during the study period, the researchers did not consider them to be treatment-related. One patient recovered from his or her AE and continued therapy, while two patients experienced fatal AEs. These included skin necrosis and infection in one patient with steroid-related immunosuppression, and pneumonia related to prior chronic lymphocytic leukemia and steroid immunosuppression in another patient.
The authors noted the study’s relatively short follow-up, lack of comparator arm, and small patient population as limitations.
“The use of fostamatinib may offer a simple option for treating wAIHA without incurring the significant side effects of prolonged corticosteroid use,” Dr. Kuter added. “Additional patients are being enrolled in this trial and will better allow us to assess the magnitude of this treatment effect and any unanticipated side effects [of fostamatinib].”
Because more than four patients achieved the primary efficacy endpoint in this phase of the study, stage two of the trial is now open for enrollment, with plans to enroll 20 more patients.
The authors report no conflicts of interest.
Kuter DJ, Arnold D, Lichtin A, et al. Fostamatinib, a spleen tyrosine kinase inhibitor, for the treatment of warm antibody autoimmune hemolytic anemia: preliminary results of the Soar phase 2, multicenter, open-label study. Abstract #S145. Presented at the 23rd Annual Congress of the European Hematology Association, June 15, 2018; Stockholm, Sweden.