Trends in Post-Relapse Survival in Classical Hodgkin Lymphoma Patients after Experiencing Therapy Failure Following Autologous Hematopoietic Cell Transplantation
Authors: Badar Talha , Epperla Narendranath , Szabo Aniko , Borson Steven , Vaughn John , George Gemlyn , Shah Nirav N , Cashen Amanda F , Hamadani Mehdi , Fenske Timothy S. 
Published: October 2019

Abstract
Background
Classical Hodgkin Lymphoma (cHL) is a highly curable disease; however, 10% of patients (pts) with limited stage and 20%-30% with advanced stage disease still fail first line-treatment. Autologous hemopoietic cell transplantation (auto-HCT) is the standard of care in pts who fail to achieve remission with first-line therapy, or who relapse after induction chemotherapy. However, approximately 50% of cHL pts will ultimately relapse post auto-HCT. These pts historically have had poor outcomes, with median survival in the 1.5 year range. In recent years, highly active new therapies such as brentuximab vedotin (BV), checkpoints inhibitors (i.e. nivolumab and pembrolizumab), and increased accessibility to allogeneic HCT (including utilization of haploidentical donors) have become more widely available. We hypothesized that, in recent years, survival has improved in cHL patients who relapse after auto-HCT since the introduction of these novel therapies into more widespread clinical practice.
Methods
We conducted a multi-center retrospective study from 3 academic institutions in the U.S. (Medical College of Wisconsin, Ohio State University, and Washington University in St. Louis) to evaluate survival of cHL pts after the failure of an auto-HCT. We reviewed 341 pts who received auto-HCT from 2006-2015. Among them, 126 (37%) pts relapsed post auto-HCT and were evaluated in more detail. For the purpose of analysis, pts were divided into 2 cohorts based on timing of auto-HCT; 2006-2010 (Cohort 1, n=57) and 2011-2015 (Cohort 2, n=69) to compare outcomes.
Results
The median age at auto-HCT, time from diagnosis to transplant, time from transplant to relapse were similar in Cohort 1 & 2 (see Table 1). The proportion of pts who achieved complete remission (CR) at the time of auto-HCT were 22.8% in Cohort 1 and 40.6% in Cohort 2. Whereas, 68.4% of pts in Cohort 1 and 52.2% of pts in Cohort 2 had partial remission (PR) at the time of auto-HCT. The median number of lines of therapy after relapse from auto-HCT were 2 each in Cohort 1 (range, 0-13) and Cohort 2 (range, 0-7), respectively (p= 0.74). Twenty-five (45%) pts in Cohort 1 and 49 (73%) pts in Cohort 2 received BV as a salvage therapy post auto-HCT (p= 0.002). Similarly, 3 (5.5%) pts in Cohort 1 versus (vs.) 21 (32%) pts in Cohort 2 received check point inhibitors as salvage therapy post auto-HCT relapse (p= <0.001). Fourteen (25%) pts in Cohort 1 and 26 (38%) pts in Cohort 2, received allogeneic HCT after relapse from auto-HCT (p= 0.10). At 5 years follow up after relapse from auto-HCT, 36.5% of pts were alive in Cohort 1 and 58.3% of pts in Cohort 2 (p= 0.03) (Fig. 1A). The proportion of pts alive at 5 years follow up from time of auto-HCT (using left truncation analysis) was 34% and not reached (NR) in Cohort 1 and Cohort 2, respectively (p= 0.02) (Fig.1B). We performed multivariate analysis for overall survival (OS) from time of auto-HCT relapse; Cohort 1 vs. 2 (HR; 0.35, 95% CI 0.18-0.65, p= 0.0009), disease status at auto-HCT (CR vs. progressive disease [PD]) (HR; 2.51, 95% CI 0.85-7.34, p= 0.01), age at auto-HCT (HR; 1.04, 95% CI 1.01-1.06, p= 0.0005) and time to relapse from auto-HCT (HR; 0.61, 95% CI 0.48-0.76, p= <0.0001), retained independent prognostic significance for OS.
Conclusion
Our analysis supports that survival of cHL pts post auto-HCT failure has significantly improved in recent years (2011-2015), most likely due to incorporation of novel therapies including BV, checkpoint inhibitors, and more widespread use of allogeneic HCT.

Disclosures
Shah: Miltenyi: Other: Travel funding, Research Funding; Juno Pharmaceuticals: Honoraria; Exelexis: Equity Ownership; Oncosec: Equity Ownership; Geron: Equity Ownership; Lentigen Technology: Research Funding. Hamadani:Celgene Corporation: Consultancy; Janssen: Consultancy; MedImmune: Consultancy, Research Funding; ADC Therapeutics: Research Funding; Takeda: Research Funding; Cellerant: Consultancy; Ostuka: Research Funding; Sanofi Genzyme: Research Funding, Speakers Bureau; Merck: Research Funding.