Novel Brentuximab Vedotin Combination Therapies Show Promising Activity in Highly Refractory CD30+ Non-HodgkinLymphoma: A Case Series and Review of the Literature

Non-Hodgkin lymphomas (NHLs) are a heterogeneous group of hematologic malignancies which typically respond to standardfirst-line chemoimmunotherapy regimens. Unfortunately, patients with refractory NHL face a poor prognosis and represent anunmet need for improved therapeutics. We present two cases of refractory CD30+ NHL who responded to novel brentuximabvedotin- (BV-) based regimens. The first is a patient with stage IV anaplastic large cell lymphoma (ALCL) with cranialnerve involvement who failed front-line treatment with cyclophosphamide, doxorubicin, vincristine, etoposide, and prednisone(CHOEP) and second line cyclophosphamide, vincristine, doxorubicin, dexamethasone alternating with high-dose methotrexate(MTX), and cytarabine (hyperCVAD) with intrathecal- (IT-) MTX and IT-cytarabine, but responded when BV was substituted forvincristine (hyperCBAD). The second patient was a man with stage IV diffuse large B-cell lymphoma (DLBCL) with leptomeningealinvolvement whose disease progressed during first-line rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone(R-CHOP) and progressed despite salvage therapy with rituximab, dexamethasone, cytarabine, and cisplatin (R-DHAP) in whomaddition of BV to topotecan resulted in a significant response. This report describes the first successful salvage treatments of highlyaggressive, double refractory CD30+ NHL using two unreported BV-based chemoimmunotherapy regimens. Both regimens appeareffective and have manageable toxicities. Further clinical trials assessing novel BV combinations are warranted