1.
Long-term efficacy of anti-PD1 therapy in Hodgkin lymphoma with and without allogenic stem cell transplantation
Manson, G., Mear, J. B., Herbaux, C., Schiano, J. M., Casasnovas, O., Stamatoullas, A., Deau, B., Schmitt, A., Garnier, G., Regny, C., et al
European journal of cancer (Oxford, England : 1990). 2019;115:47-56
Abstract
INTRODUCTION Long-term efficacy of anti-PD1 therapy and the need for a consolidation with allogenic haematopoietic stem cell transplantation (allo-HSCT) remain unclear in patients with relapsed/refractory (R/R) Hodgkin lymphoma (HL). METHODS We retrospectively analysed 78 patients with R/R HL treated with nivolumab in the French Early Access Program and compared their outcomes according to subsequent allo-HSCT. RESULTS After a median follow-up of 34.3 months, the best overall response rate was 65.8%, including 38.2% complete responses (CRs). The median progression-free survival (PFS) was 12.1 months. Patients reaching a CR upon nivolumab had a significantly longer PFS than those reaching a partial response (PR) (median = not reached vs 9.3 months, p < 0.001). In our cohort, 13 patients who responded (i.e. in CR or PR) to nivolumab monotherapy underwent consolidation with allo-HSCT. Among responding patients, none of those who underwent subsequent allo-HSCT (N = 13) relapsed, whereas 62.2% of those who were not consolidated with allo-HSCT (N = 37) relapsed (p < 0.001). There was no difference in overall survival (OS) between the two groups. Five of 6 patients who were not in CR at the time of transplantation (4 PRs and 1 progressive disease) converted into a CR after allo-HSCT. CONCLUSION Most patients with R/R HL treated with anti-PD1 monotherapy eventually progressed, notably those who did not achieve a CR. Patients undergoing consolidation with allo-HSCT after anti-PD1 therapy experienced prolonged disease-free survival compared with non-transplanted patients, but this difference did not translate into a benefit in OS. This information should be considered when evaluating the risk/benefit ratio of allo-HSCT after anti-PD1 therapy.
2.
Allogeneic hematopoietic stem cell transplantation in r/r Hodgkin lymphoma after treatment with checkpoint-inhibitors: feasibility and safety
Dada, R., Usman, B.
European journal of haematology. 2018
Abstract
OBJECTIVES Relapsed cHL patients after autologous hematopoietic stem cell transplantation (HSCT) with treatment sensitive disease are potential candidates for curative allogeneic HSCT. However, there are some concerns around performing such procedure after checkpoint inhibitors (CPIs). METHODS We collected published data of patients undergoing allogeneic HSCT after treatment with CPIs (cohort 1). Abstracts of recent conferences (2015-2017) (ASCO, ASH, EBMT, ASBMT) were also included. Results were compared with safety of recent studies (2015-2018) with allogeneic HSCT without CPIs (cohort2). RESULTS 272 records were screened. After exclusion of duplications, cohort 1 and 2 included each 6 publications with 122 and 978 patients respectively. Grade 3-4 acute GVHD in cohort 1 was found in 28% versus 8% in cohort 2 (P=0.02). Chronic GVHD was observed in 26% versus 29% respectively. NRM was 15% which remained relatively stable after 6 months of allogeneic HSCT versus 19% in cohort 2. CONCLUSIONS This is the largest pooled analysis of its kind published so far. Our results suggest that allogeneic HSCT after CPIs 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. Additional prospective studies are needed for further clarification. This article is protected by copyright. All rights reserved.
3.
Safety and efficacy of allogeneic hematopoietic stem cell transplant after PD-1 blockade in relapsed/refractory lymphoma
Merryman, R. W., Kim, H. T., Zinzani, P. L., Carlo-Stella, C., Ansell, S. M., Perales, M. A., Avigdor, A., Halwani, A. S., Houot, R., Marchand, T., et al
Blood. 2017;129(10):1380-1388
Abstract
Anti-programmed cell death protein 1 (PD-1) monoclonal antibodies are being increasingly tested in patients with advanced lymphoma. Following treatment, many of those patients are likely to be candidates for allogeneic hematopoietic stem cell transplant (HSCT). However, the safety and efficacy of HSCT may be affected by prior PD-1 blockade. We conducted an international retrospective analysis of 39 patients with lymphoma who received prior treatment with a PD-1 inhibitor, at a median time of 62 days (7-260) before HSCT. After a median follow-up of 12 months, the 1-year cumulative incidences of grade 2-4 and grade 3-4 acute graft-versus-host disease (GVHD) were 44% and 23%, respectively, whereas the 1-year incidence of chronic GVHD was 41%. There were 4 treatment-related deaths (1 from hepatic sinusoidal obstruction syndrome, 3 from early acute GVHD). In addition, 7 patients developed a noninfectious febrile syndrome shortly after transplant requiring prolonged courses of steroids. One-year overall and progression-free survival rates were 89% (95% confidence interval [CI], 74-96) and 76% (95% CI, 56-87), respectively. One-year cumulative incidences of relapse and nonrelapse mortality were 14% (95% CI, 4-29) and 11% (95% CI, 3-23), respectively. Circulating lymphocyte subsets were analyzed in 17 patients. Compared with controls, patients previously treated with PD-1 blockade had significantly decreased PD-1+ T cells and decreased ratios of T-regulatory cells to conventional CD4 and CD8 T cells. In conclusion, HSCT after PD-1 blockade appears feasible with a low rate of relapse. However, there may be an increased risk of early immune toxicity, which could reflect long-lasting immune alterations triggered by prior PD-1 blockade.