ABCL-283: A Phase I/II Trial of Brentuximab Vedotin (BV) Plus Rituximab (R) as Frontline Therapy for Patients with Immunosuppression-Associated CD30+ and/or EBV+ Lymphomas

Background: Chronic immunosuppression significantly increases the risk of developing a variety of lymphoid malignancies. Up to 80% of cases are driven by EBV-associated mechanisms of tumorigenesis. Approximately 70% will express CD30 and over 80% will express CD20. Standard-of-care rituximab (R) monotherapy followed by a response-stratified treatment approach shows poor response, with ∼75% patients requiring subsequent chemotherapy exposure; 2-year OS for the population as a whole was ∼70%. We hypothesized that a combination of brentuximab vedotin (BV) and R would yield improved breadth and depth of response compared with R monotherapy, would spare patients subsequent exposure to CIT, and result in favorable OS. Methods: Induction consisted of R 375 mg/m2 given days 1, 8, 15, and 22 and BV 1.2 mg/kg given days 1, 8, and 15 of a 28-day cycle, followed by restaging. Those with progression were removed from the study. Patients with stable disease were offered discontinuation or completion of one consolidation cycle followed by repeat assessment; consolidation was identical to induction. Patients with partial response or complete response could receive either consolidation followed by maintenance therapy (MT) or move directly to MT, which consisted of BV 1.8 mg/kg every 3 weeks and R 375 mg/m2 every 6 weeks for up to 1 year of therapy. Toxicity was defined using CTCAE 4.0, and response was assessed at the end of induction, consolidation (if given), and after cycles 4 and 7 of BV. Results: Toxicity and response data are available for 20 patients. Overall response rate was 70%, including a CR rate of 60%. Median follow-up of 26.1 months; 2-year PFS was 75%, and 2-year OS was 90%. Median time to best response was 28 days. Eighteen patients (92%) experienced toxicity at any grade with the most frequent grade 3/4 toxicities being peripheral neuropathy, neutropenia, infection, and pancreatitis. Conclusions: The combination of BV + R is effective in achieving rapid early remissions as frontline therapy for immunosuppression-related lymphomas. High toxicity rates suggest poor long-term tolerance and a different schedule or shorter treatment courses may be warranted. Further studies are needed to confirm these efficacy results and to determine optimal BV+R dosing regimens and duration.