Blood | April 9, 2021

Advani R, Moskowitz AJ, Bartlett NL, Vose J, Ramchandren R, Feldman T, LaCasce AS, Christian B, Ansell SM, Moskowitz CH, Brown L, Zhang C, Taft D, Ansari S, Sacchi M, Ho L and Herrera AF

Blood. 2021

This study was performed using a Simoa Homebrew assay.

Abstract

This phase 1–2 study (NCT02572167) evaluated brentuximab vedotin (BV) combined with nivolumab (Nivo) as first salvage therapy in patients with relapsed or refractory classical Hodgkin lymphoma. In parts 1 and 2, patients received staggered dosing of BV and Nivo in cycle 1, followed by same-day dosing in cycles 2–4. In part 3, both study drugs were dosed same day for all 4 cycles. At end of study treatment, patients could undergo autologous stem cell transplantation (ASCT) per investigator discretion. The objective response rate (N=91) was 85%, with 67% achieving a complete response. At a median follow-up of 34.3 months, the estimated progression-free survival (PFS) rate at 3 years was 77% (95% confidence interval [CI]: 65% to 86%) and 91% (95% CI, 79% to 96%) for patients undergoing ASCT directly after study treatment. Overall survival at 3 years was 93% (95% CI, 85% to 97%). The most common adverse events (AEs) prior to ASCT were nausea (52%) and infusion-related reactions (43%), all grade 1 or 2. A total of 16 patients (18%) had immune-related AEs that required systemic corticosteroid treatment. Peripheral blood immune signatures were consistent with an activated T-cell response. Median gene expression of CD30 in tumors was higher in patients who responded compared with those who did not. Longer-term follow up of BV and Nivo as a first salvage regimen shows durable efficacy and impressive PFS, especially in patients who proceeded directly to transplant, without additional toxicity concerns.