The role of checkpoint blockade after allogeneic stem cell transplantation in diseases other than Hodgkin’s Lymphoma
- 4 March 2019
- journal article
- research article
- Published by Springer Science and Business Media LLC in Bone Marrow Transplantation
- Vol. 54 (10), 1662-1667
- https://doi.org/10.1038/s41409-019-0498-0
Abstract
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curative treatment option for many malignant high-risk hematological diseases. The Graft-vs.-Tumor (GvT) effect is the major hallmark of this treatment approach. However, disease relapse remains a major limitation. Boosting the GvT effect by checkpoint inhibitors (CI) is an attractive option in this desperate situation although potentially triggering Graft-vs.-Host Disease (GvHD). Early reports in patients with Hodgkin’s lymphoma support the idea that CI therapy after HSCT is feasible and effective. We have retrospectively analyzed CI therapy for treatment of disease recurrence after allo-HSCT other than Hodgkin’s lymphoma including 21 patients from eight German transplant centers. The median follow-up was 59 days. The overall response rate (ORR) was 43%. Patients receiving donor lymphocyte infusion (DLI) in combination with CI had superior response (ORR 80%). Severe acute GvHD grade III–IV and moderate to severe chronic GvHD were observed in 29% of all patients. Taken together, CI therapy in relapsed patients after HSCT, especially in combination with DLI, is effective but induces severe GvHD in a considerable proportion of patients. Thus, prospective trials or EBMT registry-based validation of different dosing and application schedules including immunosuppressive regimens in those patients are urgently needed.Keywords
This publication has 22 references indexed in Scilit:
- Efficacy and tolerability of nivolumab after allogeneic transplantation for relapsed Hodgkin lymphomaBlood, 2017
- Clinical Implications of Genetic Mutations in Myelodysplastic SyndromeJournal of Clinical Oncology, 2017
- Tumor regression concomitant with steroid-refractory GvHD highlights the pitfalls of PD-1 blockade following allogeneic hematopoietic stem cell transplantationBone Marrow Transplantation, 2017
- PD-1 checkpoint blockade in patients with relapsed AML after allogeneic stem cell transplantationBone Marrow Transplantation, 2016
- Ipilimumab for Patients with Relapse after Allogeneic TransplantationThe New England Journal of Medicine, 2016
- Major clinical response to nivolumab in relapsed/refractory Hodgkin lymphoma after allogeneic stem cell transplantationBone Marrow Transplantation, 2016
- Quantitative characterization of T-cell repertoire in allogeneic hematopoietic stem cell transplant recipientsBone Marrow Transplantation, 2015
- Long-Term Survival and Late Deaths After Allogeneic Hematopoietic Cell TransplantationJournal of Clinical Oncology, 2011
- CTLA4 blockade with ipilimumab to treat relapse of malignancy after allogeneic hematopoietic cell transplantationBlood, 2009
- Immune escape from a graft-versus-leukemia effect may play a role in the relapse of myeloid leukemias following allogeneic bone marrow transplantationBone Marrow Transplantation, 1997