Backgrounds: Autologous hematopoietic stem cell transplantation (auto-HSCT) is the standard for relapsed/refractory classic Hodgkin lymphoma (r/r cHL) after first salvage therapy. With PD-1 inhibitors (CPI) successfully used to achieve responses before auto-HSCT, idea of delaying auto-HSCT to third- or fourth-line therapy is emerging. However, data on the impact of this shift is limited. This study aims to evaluate whether delaying auto-HSCT to the third or fourth line affects patient prognosis compared to second-line auto-HSCT after CPI.
Methods: This study included adult patients (pts) with histologically confirmed r/r cHL who underwent auto-HSCT after nivolumab-containing therapy: second-line (group 1, n=27) and third- or fourth-line (group 2, n=24). Group 1 was composed from a multicenter phase II study of nivolumab at the fixed dose 40 mg (nivo 40), followed by PET-CT assessment, and those with less than CR received two cycles of a combination therapy of nivo, ifosfamide, carboplatin, and etoposide (NICE-40, NCT04981899) before subsequent auto-HSCT. Group 2 consisted of a retrospective cohort who underwent auto-HSCT in a third- or fourth-line therapy after nivo due to either response non-achievement after first salvage therapy (58%, n=14) or patient/physician decision (42%, n=10). We hypothesized that the two groups would have similar 1-year overall and progression-free survival (1y-OS,1y-PFS) with nivo salvage regimens.
Results: A total of 51 pts were included. In group 1 (n=27), nivo 40 mg was given in all pts, with 41% (n=11) receiving nivo monotherapy and 59% (n=16) nivo followed by combination with ICE. Group 2 (n=24) received nivo at reduced dosage (40 mg and 1 mg/kg) in 71 % (n=17), while 29% (n=7) received 3 mg/kg. In group 2, 50% (n=12) received nivo combined with chemotherapy. Pre-HSCT response assessment (by LYRIC criteria) showed an objective response in 82% (CR - 63%, n=17; PR - 19%, n=5) of group 1 and 100% (CR - 96%, n=23; PR - 4%, n=1) of group 2. With a median follow-up of 11 months (1-63), survival did not differ between the groups despite a trend towards better pre-HSCT responses in group 2 (Table 1). Thus, 1y-PFS was 75% (95% CI 55-99%) in group 1 and 80% (95% CI 64-100%) in group 2 (p=0.3), and 1y-OS was 91% (95% CI 79-100%) in group 1 and 92% (95% CI 82-100%) in group 2 (p=0.9). Conclusion CPI in salvage regimens may enable auto-HSCT to be performed in the third or fourth line without affecting prognosis in terms of OS and PFS.