Successful Management of Acquired von Willebrand Syndrome Associated with Monoclonal Gammopathy of Undetermined Significance After Sotorasib Treatment in a Patient with Non-Small-Cell Lung Carcinoma.

Background

This case report investigates the effects of sotorasib treatment in a patient with acquired von Willebrand syndrome (AVWS) associated with monoclonal gammopathy of undetermined significance (MGUS), who subsequently developed non-small-cell lung carcinoma (NSCLC) with a KRAS G12C mutation. Case Presentation: The patient, a 79-year-old male, presented with a prolonged history of recurrent lower gastrointestinal bleeding attributed to digestive angiodysplasia, which had persisted for over 30 years. AVWS was suspected based on a qualitative deficiency in von Willebrand factor (VWF), with abnormal results for factor VIII activity (FVIII:C), VWF antigen (VWF:Ag), and VWF ristocetin cofactor activity (VWF:Rco) (40%, 20%, and <2.4%, respectively). Further evaluation revealed the presence of an IgM kappa monoclonal spike, suggesting MGUS. In 2022, the patient was diagnosed with NSCLC harboring the KRAS G12C mutation and initiated second-line treatment with sotorasib. Notably, one year after the initiation of sotorasib therapy, the patient's hemostasis had normalized, accompanied by significant improvements in VWF levels. VWF multimer electrophoresis demonstrated the restoration of high-molecular-weight multimers (HMWMs), and serum protein electrophoresis no longer detected MGUS.

Conclusion

These improvements were likely attributable to the indirect effects of sotorasib on the bone marrow microenvironment. By inhibiting KRAS in stromal cells and osteoclasts, sotorasib may have disrupted the supportive niche necessary for malignant plasma cell survival, resulting in a reduction in the monoclonal spike. Unfortunately, the patient eventually succumbed to carcinogenic pleurisy.