Allogeneic Stem Cell Transplantation after Exposure to Checkpoint Inhibitors: Graft Versus Host Disease and Non-Relapse Mortality in Pooled Analysis

Objectives: Relapsed cHL patients after autologous stem cell transplantation with treatment sensitive disease are usually potential candidates for curative allogeneic stem cell transplantation (HCT). However, there are some concerns around performing such procedure after treatment with checkpoint inhibitors.

Methods: We collected published data of patients undergoing allogeneic (HCT) after treatment with checkpoint inhibitors. Abstracts of recent conferences (2015-2017) (ASCO, ASH, EBMT) were also included. Results (cohort 1) were compared with safety of recent studies with allogeneic HCT in cHL (2015-2018) without prior exposure to checkpoint inhibitors (cohort2). Only studies reporting on outcome of ≥3 patients were considered. Two reviewers studied the publications independently and matched extracted data. In case of author/group duplication, the publications were jointly rescanned by the reviewers and unified decision was taken whether the reported cohorts are the same. In case of confirmed duplication, the most recent report or the one with more detailed information was chosen. End points were rates for grade 3-4 acute GVHD, chronic GVHD and Non-relapse mortality (NRM).

Results: Total of 259 records with 1100 patients were screened. Mean number of checkpoint inhibitors cycles received prior to allogeneic HCT was nine (range 1-38). Grade 3-4 acute GVHD in cohort 1 was 28% (95% CI, 20-37%) in comparison with 8% (95% CI, 6-10%) in historical cohort. Chronic GVHD was observed in 26% (95% CI, 19-36%) versus 29% (95%, CI 26-31%) respectively. In cohort 1, NRM rate was 15% (95% CI, 9-23%) which remained relatively stable after 6 months of allogeneic HCT versus 19% in cohort 2. Only 6.6% deaths were attributed to GVHD while the remaining 7.4% deaths were due to other complications of allogeneic HCT. Other relevant results will be presented at the 60^th Annual Meeting of the American Society for Hematology in December 2018.

Conclusions: This is the largest pooled analysis of its kind published so far. Our results suggest that allogeneic stem cell transplantation after checkpoint inhibitors is feasible and not associated with higher mortality. However, careful consideration should be given for prevention, early detection and effective treatment of GVHD in these cases.