Abstract P113

Dose-dense Brentuximab Vedotin Plus Ifosfamide, Carboplatin, and Etoposide (ICE) in Second Line Treatment of Relapsed/Refractory Classical Hodgkin Lymphoma: 5-year Long Term Follow Up

Background: Classical Hodgkin lymphoma (CHL) patients (pts) requiring second line therapy may still be cured with multiagent salvage chemotherapy followed by autologous stem cell transplant (ASCT). We previously published results of a phase I/II clinical trial which showed that dose-dense brentuximab vedotin (Bv) combined with ICE was highly active in this setting (Lynch RC et al, Lancet Haematology 2021) We present 5-year long term follow-up from this study (#NCT02227199).

Methods: Pts ≥ 18 years old with first relapse or primary refractory CD30+ CHL were eligible. Treatment details were previously published. Once MTD of Bv with ICE was established, subsequent pts were treated at this dose. Two 21-day cycles were given with G-CSF support. PET was performed after Cycle 2, with response assigned per Cheson 2007. The primary endpoint was to estimate the MTD and CR rate after 2 cycles. Secondary endpoints included PFS and OS.

Results: All 45 pts have enrolled and completed study treatment, including 42 pts who received treatment at the MTD of 1.5 mg/kg on day 1 and 8 of each cycle. Median age was 31 (range, 21-61). 43 pts were evaluable for efficacy. Overall response rate (ORR) and CR for all enrolled pts were 91% and 74% respectively. Among primary refractory pts, ORR and CR were and 86% and 68% respectively. Thity-seven pts proceeded with ASCT. Only 2 pts did not proceed with ASCT due to inadequate response to salvage therapy.

With an updated median follow up of 5.2 years, 5-year PFS was 77% (95% CI 66-91), and 5-year OS was 91% (82-100).

Two pts had PD post study treatment and never received an ASCT (one lost to follow up, other died after declining therapy for chronic phase CML). Five pts relapsed post ASCT, two of whom subsequently had an allogeneic transplant and are in CR. Three pts remain alive after relapse with ongoing therapy.

Five pts developed secondary malignancies, two of which were excised skin cancers (basal cell carcinoma, melanoma). Three pts developed non-skin cancers (lung adenocarcinoma, myelodysplastic syndrome, chronic phase CML) and all have succumbed to their disease.

Overall, five pts have died since enrollment on the study due to secondary cancers (3), study treatment (1), or complications of ASCT (1).

Conclusions: As the field of CHL shifts to incorporate PD1-inhibitors in the front-line setting, the Bv-ICE regimen may provide primary refractory patients a novel, effective treatment option.