Outcome of high-dose chemotherapy (HDCT) and autologous stem cell transplant (ASCT) as first salvage treatment for relapsed or refractory classical Hodgkin Lymphoma (cHL) in the era of PET-adapted strategy among Italian centers
HDCT+ASCT is still considered the standard of care for patients (pt) with cHL failing first-line treatment(FT). However data on the efficacy of HDCT+ASCT in the era of PET-driven strategy are limited.
Aim of study:
To evaluate the outcome and prognostic factors of ASCT as first salvage treatment in pt failing or relapsing after FT.
We performed a retrospective observational multicenter study on individual data of pt who underwent ASCT from 2009 to 2021 at 11 participating centers in Italy. Study endpoints were: clinical characteristics at relapse or failure, overall response rate (ORR) and complete remission (CR) to first salvage therapy (ST), number of ST before ASCT, disease-status at ASCT, 3-yr progression-free survival (PFS) and overall survival (OS) calculated from the date of ASCT, factors associated with ASCT outcome evaluated by univariate and multivariate analysis.
217 evaluable pt were enrolled; 32% of them had a positive PET-2 (PET2+) after the firs 2 cycles of ABVD and 66% switched from ABVD to intensified therapy. Main pt characteristics at relapse or progression after FT were: median age 34 years (range, 18-68), stage III/IV 46%, B symptoms 25%, bulky 4%, extranodal disease 29%, anemia 13%, ECOG PS ≥2: 9%; refractory disease (failure to achieve CR with FT or relapse ≤3 months) 48%, early relapse (< 12 months from FT end) 24%, late relapse (≥ 12 months from FT end) 28%. Before ASCT, 53% pt received 1, 31% 2 and 16% received ≥ 3 ST lines. After first ST line, ORR was 65% and mCR 45%. Overall, 67% pt underwent ASCT in CR (98% of them in mCR), 22% in partial response (PR) and 11% with stable or progressive disease. After a median follow up of 42 months (IQR,24-66) 3-yr PFS and OS were 72 (95%CI, 65-77) and 90% (95% CI, 84-93), respectively. Figure 1 shows 3-yr PFS according to response to FT. According to disease status at ASCT and number of ST lines, 3-yr PFS was significantly better for pt in CR compared to their counterpart (HR 1.79, p=.039), and for pt receiving ≤ 2 vs > 2 lines ST (HR 2.52; p=.002). PET2+ during FT was associated with a higher risk of salvage ASCT failure (HR 2.43, p=.002).
HDCT+ASCT is an effective salvage approach for pt failing a PET-guided FT, even for those with primary refractory disease. Receiving ≤2 ST lines and being in CR at ASCT confers the most favorable outcome, whereas a PET2+ in the FT seems an early unfavorable predictor for subsequent salvage ASCT procedures.