Spheroid culture to select theoretical therapeutic drugs in intravascular large B-cell lymphoma.

Intravascular large B-cell lymphoma (IVLBCL) is a rare type of extranodal large B-cell lymphoma that is characterized by the proliferation of lymphoma cells in the lumina of small vessels. Recent progress uncovering the genetic characteristics associated with MYD88/CD79B mutations has stimulated interest in the use of drugs targeting B-cell receptor signaling, including Bruton's tyrosine kinase. However, difficulties in culturing ex vivo IVLBCL cells has hampered research on the development of novel therapies. In the present study, we demonstrated the establishment of an ex vivo culture system of IVLBCL cells obtained from patient-derived xenograft (PDX) models. The spheroid culture enabled us to culture IVLBCL PDX cells for more than 10 days and to explore the efficacy of drug treatments acting on these cells. We found that carfilzomib and ibrutinib were effective for treating IVLBCL in ex vivo experiments and conducted in vivo analyses to assess the efficacy of these drugs. Although the efficacy of carfilzomib was difficult to confirm due to its toxicity in our models, ibrutinib showed comparable efficacy to a standard combination of chemotherapy drugs. Together, our data provide a new culture method for IVLBCL PDX cells and a rationale for translating ibrutinib to clinical use in IVLBCL patients.