Abstract

Background: Traditional salvage chemotherapy followed by autologous stem cell transplant (ASCT) is the standard second line approach for treatment of relapsed/refractory (r/r) Classical Hodgkin Lymphoma (cHL) and can cure approximately 50-60% of patients (pts). Novel agents such as brentuximab vedotin (BV) and check-point inhibitors (CPIs) have high response rates in the r/r setting and have recently been used as salvage regimens to induce remissions before ASCT. Limited data exists comparing efficacy of these two approaches. Aims: Our aim was to compare outcomes of pts receiving salvage chemotherapy (CT) as opposed to novel treatments (NT) for their first salvage regimen for r/r cHL. Methods: Adult pts with r/r cHL who received their first salvage regimen (SR1) between January 2018 and June 2020 were retrospectively identified across 9 academic centers in the United States. Baseline characteristics were compared across CT and NT cohorts based on SR1. Endpoints were to compare complete response (CR), overall response rate (ORR), and event free survival (EFS) between the CT and NT cohorts. ORR was defined as CR+ partial response (PR). Events were defined as stable disease (SD) or progressive disease (PD) after SR1, less than a complete response (CR) at 90 days post-ASCT, PD after ASCT, or death. Results: In total, 120 pts were identified with a median age of 33 years (range 18-85). 68% had advanced disease and 13% were early stage unfavorable (NCCN) at diagnosis. 88% received ABVD based front-line regimen. Many pts had poor prognostic characteristics including 43% with primary refractory disease, 52% with relapse <12 months from diagnosis, 38% with extranodal disease, and 26% with B-symptoms at time of relapse (Table 1). 65% of pts (n=78) received CT and 35% (n=42) received NT for SR1. 90% of CT pts received Ifosfamide, Carboplatin, and Etoposide (ICE) as SR1. Regimens used for NT treated pts included BV + Bendamustine (43%), BV alone (36%), BV + CPI (12%), BV + CT (5%), and other CPI (4%). No significant difference was found in the ORR and CR rates according to pts treated with CT vs. NT of 67% vs. 69% and 47% vs. 55%, respectively. Of the 104 patients who received ASCT, 88% received CT and 83% received NT for SR1. At a median follow-up of 32 months, 1-year EFS was 57% vs 69% and 2-year EFS was 56% vs 66% between CT and NT cohorts (p=0.25) (Figure 1). All pts who progressed after CT for SR1 (n=31) received NT for SR2; whereas 73% (n=11) of those progressing after NT for SR1 received CT for SR2. ORR for CT in SR2 was 91% vs 70% for NT (p=.48). The most common SR2 CT regimen was ICE (82%), and NT regiment for SR2 was BV alone (40%), BV + Bendamustine (31%), BV + CPI (23%), and other CPI (6%). 79% vs 89% remained progression-free post-ASCT at their last follow-up after receiving CT vs. NT at last salvage respectively (p=0.15). Of the 16 pts who did not proceed to ASCT, 7 died within an average of 19.5 months from the receipt of SR1. Interestingly, pts who did not proceed to ASCT had a significantly improved 2-year EFS if they received NT (n=7) at SR1 (71% vs. 13%) when compared to CT at SR1 (n=9) (p=0.03). Image:Summary/Conclusion: There was a numerical trend towards better CR and EFS for novel therapy compared to traditional chemotherapy for first salvage, however the outcomes were not statistically significant. This demonstrates that CT is still a useful salvage therapy that can effectively get patients to an ASCT for curative intent. Prospective studies comparing novel therapy to traditional chemotherapy for salvage are warranted.

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