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Br J Haematol. 2019 May;185(3):468-479. doi: 10.1111/bjh.15801. Epub 2019 Feb 15.

Immune off-target effects of Brentuximab Vedotin in relapsed/refractory Hodgkin Lymphoma.

Author information

1
Section of Haematology, Department of General Surgery and Medical-Surgical Specialties, University of Catania, Catania, Italy.
2
Division of Haematology, Azienda Policlinico-OVE, Catania, Italy.
3
Department of Medical and Surgical Sciences and Advanced Technologies "G.F. Ingrassia", University of Catania, Catania, Italy.

Abstract

Hodgkin Lymphoma (HL) is associated with deep microenvironment re-shaping and myeloid dysfunction. Given that only limited data are available regarding 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, we evaluated 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 HL patients. After a median of four BV cycles, the overall response rate (complete response + partial response) was 47%, with 4 (27%) complete metabolic remissions. BV reduced the absolute number of three MDSC subtypes and s-Arg-1 levels. Patients with baseline s-Arg-1 ≥200 ng/ml had inferior progression-free survival at 36 months compared to those with low s-Arg-1. T-regs dysfunction was recovered by BV: absolute T-regs count was increased after treatment with BV, independently of metabolic response achieved, with a significant reduction of CD30+ T-regs. Our data disclose off-target effects of BV in the microenvironment that could explain its deep and durable clinical efficacy.

KEYWORDS:

Brentuximab Vedotin; T-reg; arginase; myeloid-derived suppressor cells; refractory Hodgkin lymphoma

PMID:
30768678
DOI:
10.1111/bjh.15801

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