Brentuximab Vedotin Alone and in Combination with Bendamustine As Salvage Therapy for Primary Refractory or Relapsed Hodgkin Lymphoma: Multicentre Experience of the Polish Lymphoma Research Group (PLRG)
Authors: Czyz Anna , Lojko-Dankowska Anna , Joks Monika , Komarnicki Mieczyslaw , Dlugosz-Danecka Monika , Jurczak Wojciech , Rybka Justyna , Wrobel Tomasz , Paszkiewicz Ewa , Walewski Jan , Hawrylecka Dorota , Drozd-Sokolowska Joanna , Subocz Edyta , Agata Szymanska , Witkowska Magdalena , Smolewski Piotr , Kolkowska Agnieszka , Lech Maranda Ewa , Knopinska-Posluszny Wanda , Giebel Sebastian , Zaucha Jan 
Published: October 2019

Abstract
An optimal treatment for patients with primary refractory or relapsed (R/R) Hodgkin lymphoma (HL) who did not respond to standard salvage therapy has not been established. Brentuximab vedotin (BV) and bendamustine (B) used as monotherapy were shown to be active in R/R HL and both are recommended as a therapeutic option. It has been proposed that the combination of BV with B (BVB) may improve the outcome of R/R HL patients. To test this hypothesis, we compared retrospectively the efficacy and safety of BV and BVB regimen in R/R HL patients. Methods: Since March 2014 all patients with R/R HL treated at PLRG centers were offered either BV in monotherapy every 21 days or in combination with B (B 90 mg/m² on days 1 and 2 of treatment cycle) according to the policy in each center. Results: BV or BVB therapy was administered to 94 patients (median age 33 years, range 18-68) with primary refractory (n=54) or relapsed HL (n=40), including 34 patients after autologous stem cell transplant (ASCT). The patients were treated with the median of 3 (range, 2-12) prior chemotherapy lines. Fifty-seven patients received BV and 37 patients BVB regimen. In 16 of them, BVB was de-escalated to BV after the median of 2 cycles (range, 2-7). The patients' and disease characteristics did not differ between two groups. In the whole study group, the median number of applied cycles per patient was 4 (range, 2-16). Dose-limiting toxicities were observed in 8% of patients. No difference was found between BV and BVB group, with similar rate of grade 3-4 neutropenia (16% vs 13%) and thrombocytopenia (4% vs 3%). Lung infection occurred in 1 patient treated with BV (2%) and 3 treated with BVB (2% vs 8%, p ns), with 2 treatment-related deaths in the BVB group. The response rate after 2 cycles of BV and BVB treatment defined as complete (CMR) or partial metabolic response (PMR) assessed by positron emission tomography was 69% (26% of CMR and 43% of PMR) and 89% (46% of CMR and 43% of PMR), respectively (p=0.036). After 4-6 cycles of treatment, CMR, PMR and stable metabolic disease was documented in 59%, 19% and 13% in the BV group vs. 71%, 17% and 3%, respectively, in the BVB group (p ns). Finally, 36 patients (22 from BV and 14 from BVB group) proceeded to ASCT, and 17 (9 from BV and 8 from BVB group) to allogeneic SCT. The overall and progression-free survival at 24 months were 80% and 51%. The survival curves did not differ between two study groups. In conclusion, our results suggest that BVB is a feasible regimen that provides higher response rate after 2 cycles compared to BV monotherapy. However, the overall response rate achieved after 4-6 cycles of treatment are comparable between BV monotherapy and combined BVB treatment. Infectious complications, including serious lung infections, were observed in both study groups, with two treatment-related deaths in the BVB group.

Disclosures
Dlugosz-Danecka: Roche: Consultancy; Servier: Consultancy. Jurczak:Nordic Nanovector: Research Funding; Epizyme: Research Funding; Beigene: Research Funding; Bayer: Research Funding; Celgene: Research Funding; Merck: Research Funding; Servier: Consultancy, Honoraria, Research Funding; European Medicines Agency: Consultancy; AstraZeneca: Consultancy; Gilead: Consultancy, Research Funding; Afimed: Research Funding; Morphosys: Research Funding; Janssen: Consultancy, Research Funding; Sandoz-Novartis: Consultancy; Roche: Research Funding; Pharmacyclics: Research Funding; Acerta: Consultancy, Research Funding; TG therapeutics: Research Funding. Zaucha:Roche: Honoraria; Takeda: Honoraria; Amgen: Honoraria; Celgene: Honoraria.