Obinutuzumab Induced ITP:a Case Report

Obinutuzumab induced ITP:

Introduction

Obinutuzumab is a monoclonal antibody that targets the CD20 antigen expressed on the surface of pre-B and mature B-lymphocytes. Upon binding to CD20, obinutuzumab mediates B-cell lysis through engagement of immune effector cells and the immune effector cell mechanisms which include antibody dependent cellular cytotoxicity and antibody dependent cellular phagocytosis. Obinutuzumab is known to cause an acute thrombocytopenia in 5% of patients where there is a rapid drop in platelets within first 24 hours of infusion which could be an immune related phenomenon. We present a case of Obinutuzumab induced thrombocytopenia which was treated as ITP thus further implicating autoantibodies as the pathophysiologic mechanism.

Case- An 80-year-old female with a history of diffuse large B-cell lymphoma who had previously received Rituximab mini CHOP for 6 cycles with complete metabolic response relapsed 2 months later and had widespread progression. She was then treated with second-line therapy with Polatuzumab and Bendamustine along with rituximab for cycles after which the bendamustine was removed for the final 6 cycles to ensure she was a candidate for Car-T therapy. Posttreatment PET scan showed a new areas of brain metastatic disease in the right frontal lobe as well as the mediastinum and lung parenchymal worrisome for recurrence of lymphoma. The patient has been started on obinutuzumab. After first cycle of Obintazumab on 7/3/2022. she developed severe thrombocytopenia with a platelet count less than 10,000/ul. All of the work up including hemolysis labs, HIT, viral, and nutritional panel was negative and diagnosis of ITP as diagnosis of exclusion was made. A BM biopsy was performed on 7/5/2022 and did not have any evidence of acute leukemia, lymphoma, or dysplasia. Treatment has been started for ITP and patient has been started on Prednisone 1mg/kg on daily basis and IVIG 1g/kg for doses. After these interventions, counts has been recovered to >50 in next 3-4 days.

Discussion

Obinutuzumab has been routinely used in those with progression of B cell lymphoproliferative disease refractory to rituximab. While thrombocytopenia is a common complication observed with the first Obinutuzumab administration, it is commonly seen a few days after infusion. However, developing grade 3-4 thrombocytopenia within the first 24 hours remains a rare occurrence. It is unclear whether this is caused by direct toxicity to platelets and megakaryocytes or antibody mediated destruction. Some case reports have observed without therapy until hematological recovery and supportive transfusion during this period. However, our patient remained refractory to transfusion indicating possible immune component resulting in ITP. In such, we used IVIG and glucocorticoid therapy to halt platelet destruction and assist platelet count stabilization and recovery. This case highlights the benefit of ITP like therapies and thus raises the possibility that the acute thrombocytopenia within the first 24 hours after administration of obinatuzumab may be immune mediated.

Liles:Vifor: Other: presently and the Sub I or PI on trials; Biogene: Other: presently and the Sub I or PI on trials; Novartis: Other: presently and the Sub I or PI on trials; Takeda: Other: presently and the Sub I or PI on trials; Shire,: Other: presently and the Sub I or PI on trials; Incye,: Other: presently and the Sub I or PI on trials; Apellis: Other: presently and the Sub I or PI on trials; Sun Pharma: Other: presently and the Sub I or PI on trials; Momenta pharmaceuticals: Other: presently and the Sub I or PI on trials; PiCori: Other: I also am the Site Sub I for 2 PiCori grants in sickle cell anemia..