PB1341 - Obinutuzumab-induced thrombocytopenia: an under-recognized immunotherapy related thrombocytopenia

Background: Obinutuzumab, a third-generation anti-CD20 monoclonal antibody (mab), is widely used in the treatment of B-lymphoproliferative disorders (B-LPD). Therapy is associated with an unusually sudden thrombocytopenia which can be severe, life-threatening, and may occur as short as 1-hour post-administration. The pathophysiology is unclear, but an immune component is postulated. The diagnosis is always challenging as obinutuzumab is usually administered in combination with myelosuppressive therapies for diseases which may themselves infiltrate the bone marrow. The optimal management is unresolved but cases usually resolve spontaneously some time after cessation.

Aims: To present a case series of obinutuzumab-induced thrombocytopenia with a review of the literature

Methods: Retrospective case series of all known instances in Canberra Australia from November 1, 2021, to November 1, 2022.

Results: Four patients with B-LPDs treated with chemoimmunotherapy developed thrombocytopenia within 28 days post-obinutuzumab administration. One patient was given steroids and intravenous immunoglobulin whereas thrombocytopenia resolved after obinutuzumab withdrawal in the remaining cases (3/4).

In one patient who also received venetoclax, this was initially postulated as the cause of thrombocytopenia and hence suspended as per clinical guidelines. As depicted in figure 1, this had no effect on the platelet count hence obinutuzumab was suspended and venetoclax resumed. This was followed by a steady platelet recovery. Obinutuzumab rechallenge led to acute thrombocytopenia (4 x 10^9/L) two days later. Cessation of obinutuzumab again led to a steady platelet recovery.

Conclusion(s): Increased physician awareness of this phenomenon is required. Correlating the timing of exposure with thrombocytopenia is most important to assist in diagnosis. Obinutuzumab rechallenge may be considered in the absence of bleeding with prior instances. Future work is needed to understand the mechanism of such accelerated platelet destruction and guide detection and management strategies given the increasing reliance on mab for many solid and hematological cancers.