Improved outcomes of high-risk relapsed Hodgkin lymphoma patients after high-dose chemotherapy: a 15-year analysis

Abstract

High-dose chemotherapy and autologous stem-cell transplant (HDC/ASCT) is standard treatment of chemosensitive relapsed classical Hodgkin lymphoma (cHL), although outcomes of high-risk relapse (HRR) patients remain suboptimal. We retrospectively analyzed all HRR cHL patients treated with HDC/ASCT at our institution between 01/01/2005-12/31/2019. HRR criteria included primary refractory disease/relapse within 1 year, extranodal extension, B symptoms, requiring > 1 salvage line, or PET+ disease at ASCT. All patients met the same ASCT eligibility criteria. We treated 501 patients with BEAM (N=146), BuMel (N=38), GemBuMel (N=189) and vorinostat/GemBuMel (N=128). The GemBuMel and vorinostat/GemBuMel cohorts had more HRR criteria and more patients with PET+ disease at ASCT. Pre-ASCT BV, anti-PD1, PET-negative disease at ASCT, and maintenance BV increased over time. BEAM and BuMel predominated in earlier years (2005-2007), GemBuMel and BEAM in middle years (2008-2015), and vorinostat/GemBuMel and BEAM in later years (2016-2019). Median follow-up is 50 months (6-186). Outcomes improved over time, with 2-year PFS/OS rates of 58%/82% (2005-2007), 59%/83% (2008-2011), 71%/94% (2012-2015) and 86%/99% (2016-2019) (P

Anti-PD1 Consolidation in Patients with Hodgkin Lymphoma at High Risk of Relapse after Autologous Stem Cell Transplantation: A Multicenter Real-Life Study

“…The management of patients with RR-HL is constantly evolving in the modern era [ 42 ]. The incorporation of novel agents, such as BV and PD1-blockers, in earlier treatment lines up to the frontline therapy, is generating significant changes in the strategic approach to patients with RR-HL [ 8 , 14 , 19 , 43 ]. While the survival outcomes of post-ASCT relapses are currently superior to those achieved over the last decade, there is still room for additional improvements [ 13 , 14 , 44 ].…”

“…The incorporation of novel agents, such as BV and PD1-blockers, in earlier treatment lines up to the frontline therapy, is generating significant changes in the strategic approach to patients with RR-HL [ 8 , 14 , 19 , 43 ]. While the survival outcomes of post-ASCT relapses are currently superior to those achieved over the last decade, there is still room for additional improvements [ 13 , 14 , 44 ]. In this scenario consolidation with PD-1 blockers may represent a further promising approach to counteract the risk of post-ASCT recurrence in specific subsets of patients.…”

“…Recently, the historically grim outlook of these patients has been markedly improved by the introduction of CD30-targeted agents, such as brentuximab vedotin (BV), and programmed cell death-1 (PD-1)-blockers, including Nivolumab and Pembrolizumab [ 11 , 12 , 13 , 14 ]. In particular, the unique biology of HL renders this tumor the most responsive malignancy to PD-1 blockade.…”

“…Patients given BV or PD1-blockers after ASCT failure can achieve progression-free survival (PFS) rates approaching 2 years and 5-year overall survival (OS) rates up to 70–80% [ 11 , 14 , 15 , 16 , 17 , 18 ]. Then, different approaches were pursued to employ BV and PD-1 blockers to prevent ASCT failure, including early use in patients with a PET-positive status after salvage chemotherapy, application as single agents, followed by chemotherapy in case of an inadequate response pre-ASCT, direct integration into salvage regimens and combined use of BV and anti-PD1 antibodies as a ‘no chemotherapy salvage’ [ 12 , 19 , 20 , 21 , 22 , 23 ].…”

Tumor Immune Microenvironment in Lymphoma: Focus on Epigenetics

“…Chemotherapy has improved the outcomes of lymphoma patients over the immunophenotypic subgroups and is the standard treatment for those patients, together with other treatments such as radiation, stem cell transplantation, targeted therapies, or immunother-apies [32][33][34]. Immunotherapy has become a tool for lymphoma treatment as it restores the anti-tumor response of the patient's immune system.…”