Fostamatinib More Effective Earlier in Treatment for Immune Thrombocytopenia

Fostamatinib, a spleen tyrosine kinase (SYK) inhibitor, was more effective and had similar safety when used as a second-line therapy, rather than as a third-line or later therapy, in adults with immune thrombocytopenia (ITP), a study published in the British Journal of Haematology suggests. The authors, led by Ralph Boccia, MD, from the Center for Cancer and Blood Disorders in Bethesda, Maryland, added that platelet count responses, once achieved, were durable – irrespective of number of prior lines of therapy.

In this report, Dr. Boccia and investigators hypothesized that early treatment of ITP with SYK inhibition may interrupt disease progression by blocking phagocytosis of antibody-coated platelets, and thus subsequent thrombocytopenic events. They conducted a post hoc analysis of patients enrolled in the phase III FIT-1 and FIT-2 clinical trials, as well as the open-label extension FIT-3 study, to compare the rates of platelet response according to line of therapy (second vs. third or later) and disease stage (persistent vs. early or late chronic ITP).

Of the 145 patients from FIT-1 and FIT-2 included in this analysis, 32 received fostamatinib as a second-line therapy and 113 received it as third-line or later therapy. The median ages at baseline were 50 years in the second-line group and 54 years in the third-line or later arm.

Patients who received fostamatinib as second-line therapy did so following only steroids with or without intravenous immunoglobulins. In the third-line or later group, fostamatinib was administered after at least one second-line treatment, which included steroids with or without immunoglobulins, rituximab, splenectomy, thrombopoietin receptor agonist, cyclosporin, azathioprine, mycophenolate mofetil, vincristine, or dapsone. The median number of prior second-line therapies in this subgroup was four (range = 2-14).

Fostamatinib was more effectively, and as safely, used as second-line therapy for ITP compared with later lines, but additional studies are needed to confirm these findings.

A platelet response of ≥50×109/L or ≥30×109/L at any visit (without the need for rescue therapy within 4 weeks) was the study’s main efficacy endpoint. Researchers also calculated the durability response as the percentage of treatment days where response was maintained.

The investigators observed platelet responses of ≥50×109/L in 25 of 32 patients (78%) with fostamatinib as a second-line therapy, compared with 54 of 113 patients (48%) when fostamatinib was administered as third-line or later therapy.

Proportions of patients achieving a platelet response declined with each additional previous therapy line:

  • third-line: 64%
  • fourth-line: 52%
  • fifth-line: 36%

Overall, 54% of patients in the study population achieved at least one platelet count ≥50×109/L with fostamatinib treatment. Most responders (81%) attained ≥50×109/L within a 12-week period of initiating fostamatinib, including 76% of second-line responders – 56% of whom responded within 4 weeks.

Treatment responses were maintained for long periods of time, the authors observed. In the second-line group, patients had a response for a median of 83% of treatment days (median = 33 months). As third-line or later, fostamatinib response was maintained for a median of 86% of treatment days (median = 13 months). A similar proportion of second-line (64%) and third-line or later (63%) responders had platelet responses consistently at or above 50×109/L.

When looking at response according to time from diagnosis, the proportion of patients with responses ≥50×109/L appeared to drop with longer disease duration: Nine of the 10 patients who had persistent ITP responded (90%), compared with 11 of the 19 patients with 1 to 2 years of ITP (58%) and 59 of the 116 patients with 2 to 53 years of ITP (51%).

Safety profiles were similar between patients who received fostamatinib as second-line and third-line or later therapy, Dr. Boccia reported. However, a greater proportion of patients who received fostamatinib as third-line or later experienced an adverse event (AE) during the study period (94% vs. 72%). Severity of AEs in the second-line and third-line or later group were as follows:

  • mild: 16% vs. 24%
  • moderate: 22% vs. 45%
  • severe: 34% vs. 25%

Platelet responses also appeared to lead to lower rates of bleeding events, the investigators reported, as fewer patients in the second-line group experienced any bleeding event (28% vs. 45%).

The authors concluded that fostamatinib was more effectively, and as safely, used as second-line therapy for ITP compared with later lines, but noted that additional studies are needed to confirm these findings and to explore whether fostamatinib may prevent disease progression.

A limitation of this analysis included the lack of random allocation of lines of therapy prior to fostamatinib initiation. The small number of patients in the second-line therapy group further limit the findings.

Study authors report relationships with Rigel Pharmaceuticals, which sponsored this trial.


Boccia R, Cooper N, Ghanima W, et al. Fostamatinib is an effective second-line therapy in patients with immune thrombocytopenia. Br J Haematol. 2020;190:933-938.