Romano A, et al. - Researchers sought to ascertain the role of brentuximab vedotin (BV) as single agent in transplant-naive relapsed/refractory (R/R) patients and its off-target effects on immune system via assessing the amount of regulatory T-cells (T-regs), myeloid-derived suppressor cells (MDSC) subpopulations, and their functional marker, serum arginase-1 (s-Arg-1), in peripheral blood of 15 consecutive R/R Hodgkin lymphoma (HL) patients. Reduction in the absolute number of three MDSC subtypes and s-Arg-1 levels was observed in correlation with BV reception. They observed inferior progression-free survival at 36 months among patients with baseline s-Arg-1 ≥200 ng/ml compared to those with low s-Arg-1. BV led to the recovery of T-regs dysfunction: absolute T-regs count was increased after treatment with BV, irrespective of metabolic response achieved, with a significant reduction of CD30⁺T-regs. These findings regarding the off-target effects of BV in the microenvironment may explain its deep and durable clinical efficacy.