Nonresponse to Rituximab in Immune Thrombocytopenia

David Green, MD, PhD

In nonresponders, T lymphocytes are activated and platelet destruction is triggered, mainly in the spleen.

Rituximab, an antibody against CD20 on B lymphocytes, is often selected for the treatment of immune thrombocytopenia (ITP) that is refractory to corticosteroids. Response to rituximab occurs in up to 40% of patients, allowing them to avoid urgent splenectomy and other therapies. However, rituximab has some serious toxicities and is costly, and the reasons for treatment failure are unclear.

To examine features of ITP associated with nonresponse to rituximab, an investigative team examined the spleens of 12 ITP patients refractory to rituximab, 11 ITP patients never treated with the drug, and 9 controls without ITP undergoing splenectomy.

Results showed that in rituximab nonresponders:

• The ratio of splenic T-suppressor cells (Th1) to T-regulatory cells is increased compared with untreated patients and controls.
• Splenic effector memory T cells are increased compared with untreated patients and controls.
• Splenic cytotoxic T-suppressor cells are activated and migrate to the red pulp where they are in close proximity to platelets; platelets are seen in macrophages.
• Activated T cells are not found in the peripheral blood.

Citation(s):

Audia S et al. Preferential splenic CD8+ T-cell activation in rituximab-nonresponder patients with immune thrombocytopenia. Blood 2013 Oct 3; 122:2477.