Combination treatment with thrombopoietin receptor agonists (TPO-RA), immunosuppressants, and intravenous immunoglobulin G (IVIG) appears to be efficacious in the management of patients with severe refractory immune thrombocytopenia (ITP), according to a study published in the British Journal of Haematology.
Researchers evaluated the combination of ciclosporin A and mycophenolate mofetil (CSA/MMF; to inhibit T-cell activation), romiplostim or eltrombopag (to stimulate platelet production), and IVIG (to inhibit autoantibody-mediated platelet destruction) as a way to target 3 different mechanisms of ITP pathology.
The retrospective study assessed safety and efficacy in both children and adults who did not respond to first- or second-line treatments. The primary end point was increased platelet count (> 30 x 109/L). The secondary end point was a reduction in dose or frequency of IVIG infusions or of romiplostim or eltrombopag.
The researchers identified 18 patients (6 pediatric; 12 adult) who were unresponsive to monotherapy with TPO-RAs or IVIG at the Platelet Disorders Center at Weill Cornell Medicine in New York. Median patient age was 40 years (range, 1-77). On average, patients had received 6.5 prior treatments (range, 3-14).
For the primary end point, 13 patients achieved increased platelet count and were considered responders. For the secondary end point, 6 patients were able to move to lower TPO-RA doses, and 1 patient was able to discontinue romiplostim. Additionally, 5 responders were able to discontinue IVIG after starting CSA/MMF with a TPO-RA, and 3 patients were able to reduce IVIG frequency or dose.
Eleven patients experienced headaches or abdominal discomfort. One pediatric patient acquired hypogammaglobulinemia after rituximab treatment. Two adult patients had bleeding symptoms during the combination treatment. One patient who had pre-existing hypertension experienced a clinically significant increase in blood pressure that resolved with ciclosporin discontinuation.
“All patients were treated before fostamatinib became commercially available,” added the researchers. “If fostamatinib, which also blocks phagocytosis, can [be used as a] substitute for IVIG, the treatment would be facilitated by no longer needing IVIG management. Once treatment is established, if a response is seen, 1 or more agents can be tapered slowly.”
- Gudbrandsdottir S, Leven E, Imahiyerobo A, Lee CS, Bussel J. Combination of thrombopoietin receptor agonists, immunosuppressants and intravenous immunoglobulin as treatment of severe refractory immune thrombocytopenia in adults and children [published online February 24, 2020]. Br J Haematol. doi: 10.1111/bjh.16426