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.
Polina Kotselyabina, Evgenia Borzenkova, Andrey Chekalov, Kirill Lepik, Liudmila Fedorova, Artem Ivanov, Elena Lepik, Elena Kondakova, Ivan Moiseev, Natalia Mikhailova, Alexander Kulagin