Tivozanib-Induced Immune Thrombocytopenia in Metastatic Renal Cell Carcinoma: A Case Report and Review
Authors: Hakem Zadeh Farigol , Iyer Uma G. 
Published: December 2024

Introduction
Renal cell carcinoma (RCC) is a commonly diagnosed cancer globally, often presenting with metastases. Treatment approaches have evolved from chemotherapy to targeted therapies and immunotherapy, significantly improving outcomes. Tyrosine kinase inhibitors (TKIs), targeting VEGF and mTOR pathways, have notably enhanced progression-free survival (PFS) and overall survival (OS). Tivozanib, a highly selective TKI inhibiting VEGFR 1, 2, and 3, is recognized for its efficacy and tolerability in advanced RCC compared to earlier VEGFR inhibitors. Despite past regulatory challenges, tivozanib has been established as an effective treatment option, particularly for patients ineligible for immune checkpoint inhibitors (ICIs). However, there is a need for considering side effects when administrating this medication in cancer patients. This case report represents one of the initial documented cases detailing the observation of severe Drug-induced immune thrombocytopenia after the initiation of tivozanib treatment in a patient.
Case Presentation
A 52-year-old male with a history of diabetes mellitus, recent pulmonary embolism on apixaban, and metastatic RCC presented with worsening shortness of breath and hemoptysis three months after initiating tivozanib treatment. He was found hypoxic and severely thrombocytopenic upon evaluation, prompting admission for further investigation. Imaging revealed a nearly collapsed left lung with suspected masses. Despite normal renal and neurological function, he exhibited petechial rash and acute thrombocytopenia, leading to suspicion of ITP secondary to tivozanib. Tivozanib was initially discontinued. Patient platelet did not recover after 5 units of platelet transfusion. Therefore, patient was started on dexamethasone, and intravenous immunoglobulin (IVIG). With the initiation of IVIG and administration of three more units of platelets, the patient's platelet count recovered. This response confirmed the diagnosis of ITP.
Discussion
Tivozanib, a TKI used in the treatment of RCC, has been associated with thrombocytopenia as a notable side effect. In real-world studies, the incidence of thrombocytopenia with tivozanib alone was found to be around 2%. Importantly, few patients on tivozanib required dose reductions or interruptions due to thrombocytopenia. Severe cases (grade 3/4) of thrombocytopenia were rare across these studies. However, when tivozanib is used in combination therapies, such as with everolimus or temsirolimus, the incidence of severe thrombocytopenia appears to increase. Management in such cases typically involved dose adjustments or interruptions to mitigate these effects. Diagnosis of tivozanib-induced ITP, similar to our patient case, involves excluding other causes of thrombocytopenia and considering the temporal relationship between drug initiation and onset of symptoms. Testing for drug-specific antiplatelet antibodies can confirm the diagnosis, although this testing may not be widely available.
Conclusion
In conclusion, in this case report, we described an incident of tivozanib-induced ITP which suggests that future monitoring of cancer patient placed on TKIs may be an essential step in their care. We also recognize that the future direction of tivozanib-induced ITP can be directed toward understanding the exact mechanism/antibodies involved in triggering such a devastating response with the goal of further advancing patient care and safety.