Improved Treatment Outcomes for Patients with Hodgkin Lymphoma Relapsing after Autologous Hematopoietic Stem Cell Transplantation in the Brentuximab Vedotin Era - the Real-Life Report from the Polish Lymphoma Research Group
Authors: Czyz Anna , Lojko-Dankowska Anna , Giza Agnieszka , Dlugosz-Danecka Monika , Jurczak Wojciech , Romejko-Jarosinska Joanna , Paszkiewicz Ewa , Rybka Justyna , Drozd-Sokolowska Joanna , Subocz Edyta , Czerw Tomasz , Nasilowska-Adamska Barbara , Kolkowska Agnieszka , Joanna Manko , Hawrylecka Dorota , Knopinska-Posluszny Wanda , Agata Szymanska , Gil Lidia , Komarnicki Mieczyslaw , Hus Marek , Walewski Jan , Giebel Sebastian , Wrobel Tomasz , Zaucha Jan 
Published: November 2019

Background
Brentuximab vedotin (BV) is an effective salvage treatment in patients with relapsing/progressive Hodgkin lymphoma (HL). However, it is unclear how much BV improved the outcome of BV naïve patients who relapsed after autologous hematopoietic stem cell transplantation (autoHCT) in real life. To address this question, we compared the outcome of patients who received conventional salvage treatment before the BV era to those who were treated with BV in haematological centres allied within the Polish Research Study Group. The goals of the study were to compare: the response rates to the conventional salvage chemotherapy and to the BV-based treatment, the proportion of patients proceeding to subsequent allogeneic (allo) or second autologous HCT and finally the overall survival (OS), and progression-free survival (PFS) of relapsing patients after autoHCT treated with and without BV.
Methods and study group
The study group consisted of adult patients with classical HL relapsing after first autoHCT who were treated either with conventional salvage chemotherapy (between 2001 and 2013; Group 1, n=121) or BV based treatment (between 2012 and 2018; Group 2, n=44). The groups did not differ in terms of age or gender. The patients in Group 2 received more chemotherapy lines before post-transplant salvage treatment (median 3, range 1-6) compared to those in historical Group 1 (median 2, range 1-6) (p=0.013). No patient was treated with immune check points inhibitors. The response to salvage treatment in the majority of patients in historical Group 1 was assessed with conventional computer tomography (CT), while in all patients in Group 2 with CT combined with positron emission tomography.
Results
The rate of the objective response rate defined as the complete or partial response was higher in Group 2 (84% vs 60%, p<0.001). Of a total of 121 patients in Group 1, 34 (28%) proceeded to the second autoHCT, and 27 (22%) to alloHCT, compared to 4 (9%) and 20 (45%) of 44 patients in Group 2, respectively (p=0.004). The median follow-up time of survivors is longer in the historical Group 1 compared to Group 2 (40 months vs 19 months, p <0.001). However, at 2 years after the start of post-transplant salvage treatment, the estimated OS for patients in Group 1 was 55.2 % (95 % CI 45.8-64.3 %) compared to 81.9 % (95 % CI 66.5-91.2 %) for patients treated with BV (p=0.009) (figure). The respective estimated 2-year PFS was 41.2% (95 % CI 32.3-50.8 %) for Group 1 and 56.2% (95 % CI 38.5-72.4 %) for Group 2 (p=0.038). Importantly, the OS of patients who proceeded to alloHCT after BV-based salvage treatment was statistically significantly better compared to patients treated with alloHCT in the historical pre-BV group (2-year OS 81% vs 55%, p< 0.001).
Conclusions
In the era of brentuximab vedotin, significantly more patients with HL relapsing after autoHCT achieve objective response and proceed to allogeneic HCT. This most likely translates to the better PFS exceeding 24 months and most importantly to the significantly better OS of patients treated with BV compared to those treated with conventional salvage chemotherapy in the pre-BV era.
Figure

Disclosures
Czyz: Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees. Dlugosz-Danecka:Roche: Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; Macrogenomics: Research Funding; Servier: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Jurczak:Gilead: Research Funding; Sandoz: Membership on an entity's Board of Directors or advisory committees, Research Funding; Incyte: Research Funding; Roche: Research Funding; Servier: Research Funding; MorphoSys: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Loxo: Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Research Funding; AstraZeneca: Membership on an entity's Board of Directors or advisory committees, Research Funding; TG Therapeutics: Research Funding; Novo Nordisk: Research Funding; Bayer: Research Funding; Celtrion: Research Funding. Walewski:Gilead: Other: Travel Expenses; Bristol-Myers Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Expenses, Research Funding; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Servier: Honoraria; Takeda: Honoraria, Research Funding; GlaxoSmithKline: Research Funding; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees. Wrobel:Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees. Zaucha:Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees.