Survival for Relapsed/Refractory Hodgkin Lymphoma Patients with Recurrent or Persistent Disease Following Autologous Hematopoietic Stem Cell Transplantation Treated in the Modern Era
Authors: Rajeeve Sridevi , Shah Gunjan L. , Moskowitz Craig H. , Moskowitz Alison J. 
Published: October 2019

Abstract
Background: We previously reported that the median survival for patients (pts) with relapsed or refractory Hodgkin lymphoma (RRHL) and persistent or recurrent disease following autologous hematopoietic stem cell transplantation (AHCT) was 25 months (Moskowitz, et al. BJH 2009). Since the advent of novel immunotherapeutic and chemotherapeutic agents for RRHL, treatment paradigms have undergone significant transformation. We sought to estimate the survival trends in the modern era for RRHL pts treated with brentuximab vedotin (BV) and/or checkpoint inhibitors (CPIs) for persistent or recurrent disease after AHCT
Method: Consecutive pts with RRHL who underwent AHCT from 2008-2015 at Memorial Sloan Kettering Cancer Center (MSKCC) were identified and included if they relapsed or had refractory disease after AHCT, confirmed by biopsy. Overall survival (OS) was estimated from the time of post-ASCT relapse using the Kaplan-Meier method. The significance of potential prognostic factors was assessed using log-rank tests.
Results: 186 pts with RRHL underwent AHCT at MSKCC between 2008-2015. 46 pts relapsed or had refractory disease after AHCT, of whom 12 pts were excluded due to incomplete follow-up. Of the remaining 34 pts, there were 19 (55%) males and 15 (44%) females. Median age was 40 years at ASCT (range 21-66 years) and 18 (53%) had primary refractory disease. The median time to relapse after AHCT was 7.3 months (range 2-109 months).
Eleven patients (32.3%) received BV as part of their salvage regimen prior to AHCT. Following post-AHCT relapse, 21 (62%) received BV, of whom 13 (38.2%) achieved complete remission (CR), 2 achieved partial remission (PR), and 6 experienced progression of disease (POD). No pts received CPIs before AHCT, and 13 (38.2%) received CPIs following post-AHCT relapse. Responses to CPI included 1 CR and 10 (80%) PRs. Median duration of CPI therapy was 15 months (range, 2-45+ months). With regard to second transplant, 13 (38.2%) pts proceeded to allogeneic hematopoietic stem cell transplantation (alloHCT). Following alloHCT, 7 (53.8%) pts are alive without disease after a median of 4 years follow-up (range, 2-10 years). In addition, 1 pt is alive with active disease, 1 pt died due to POD, and 4 (30%) died from transplant complications.
Median OS after post-ASCT relapse was 35.2 months [Figure 1]. As expected, inclusion of either BV or CPI in the post-ASCT salvage regimen resulted in significantly longer survival (2-year OS 82% vs 42%, p<0.001) [Figure 2]. OS was not significantly impacted by treatment with alloHCT, presence of refractory disease, stage, or other clinical factors.
Conclusions: Availability of BV and CPIs for RRHL has significantly improved survival for RRHL. Among pts treated with either BV or CPI at post-AHCT relapse, median survival was not reached and 82% of pts are expected to survive at least 2 years after relapse. These data serve to benchmark the expected survival for RRHL pts treated with modern-era therapy.

Disclosures
Shah: Janssen: Research Funding; Amgen: Research Funding. Moskowitz:Pharmacyclics: Research Funding; Merck & Co: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; Celgene: Consultancy; Seattle Genetics: Consultancy, Research Funding. Moskowitz:ADC Therapeutics: Research Funding; Bristol Myers-Squibb: Consultancy, Research Funding; Merck: Research Funding; Incyte: Research Funding; Takeda: Honoraria; Seattle Genetics: Consultancy, Honoraria, Research Funding.