Clinical Observation of Camrelizumab (CAM) Combined with Bendamustine and Gemcitabine (BeGe) in Relapsed/Refractory Classical Hodgkin Lymphoma (cHL): A Phase II Trial

Background

The cure rate of classical Hodgkin's lymphoma (cHL) is more than 80%. However, 20% or so of cHL patients have refractory or recurring disease, making clinical treatment complex and challenging. Currently, the standard treatment for patients with r/r-cHL is high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (HDCT/ASCT). However, the complete response rate of traditional salvage chemotherapy is not ideal, which prevents some patients from receiving stem cell transplantation. In recent years, with the application of new drugs such as PD1 inhibitors, the efficacy of R/R cHL has been further improved. we designed a prospective, single-arm, multi-center trial to evaluate the efficacy and safety of PD-1 antibody camrelizumab combined with bendamustine and gemcitabine（BeGe）in patients with relapsed or refractory (r/r) classical Hodgkin Lymphoma (cHL).

Methods

This research is a phase 2 exploratory, open-label, multi-center study. Key inclusion criteria include age≥18 and ≤75, ECOG<2, R/R cHL who had received at least first-line chemotherapy, at least one measurable lesion per Lugano criteria 2014, and preparing to receive autologous stem cell transplantation (ASCT). Patients were treated with camrelizumab (CAM, 200 mg IV, day 1 q3w) combined with bendamustine （90mg/m², IV, day 2 and Day3) and gemcitabine (1000 mg/m² day 1 and day4) for 2 cycles. Patients with complete response (CR) underwent autologous hematopoietic stem cell transplantation after high-dose chemotherapy (HDT/ASCT). Patients who did not achieve CR underwent HDT/ASCT if CR was attained after two additional cycles of CAM plus BeGe. 1-2 cycles of CAM monotherapy were permitted for individuals who were waiting more than 4 weeks for ASCT. The primary endpoint was the proport ion of patients who achieved PET-CT-confirmed complete response (CR) according to Lugano 2014 criteria.

Results

17 individuals were enrolled between February 2022 and May 2023, including 5 relapsed and 12 refractory patients. 14 (82.4%) of the enrolled patients were younger than 60 years old, with a median age of 37 years (range: 20-62) and 76.5% male. 12 patients had received first-line prior therapy, and 5 patients had received second-line therapy or more. After 2 cycles CAM plus BeGe, Overall response rate (ORR) was 94.0% (16/17) with CR rate of 64.7% (11/17) and PR rate of 29.4% (5/17). Only one patient withdrew from the study because to progressive disease (PD). 4 patients who achieved PR received 2 additional cycles of CAM plus BeGe, and 2 patients achieved CR. Up to now, autologous hematopoietic stem cell transplantation has been carried out in 7 patients, with stem cell being collected from 5 patients after 2 cycles and 2 patients after 4 cycles. With a cutoff date of June 10, 2023, the 1-year (progression-free survival) PFS rate was 86.3% and the 1-year (overall survival) OS rate was 94.1%. One patient experienced grade 3 pancreatitis. Grade 1-2 AE occurred in 9 patients, and common AEs included pruritus(4/17), pyrexia(4/17), bone marrow suppression(2/17), nausea(1/17), diarrhea(1/17), mild reactive cutaneous capillary endothelial proliferation(RCCEP, 1/17). No grade 4 or above AEs occurred.

Conclusion

It is well known that refractory cases are more difficult to treat and have a worse prognosis than relapsed cases. Despite the preponderance of refractory cases in this study, the response was excellent. Therefore, Camrelizumab combined with BeGe chemotherapy patients shows encouraging clinical efficacy and safety in R/R HL, and has no significant effect on stem cell collection, which is worthy of further study.