The role of checkpoint blockade after allogeneic stem cell transplantation in diseases other than Hodgkin's Lymphoma

TY - JOUR

T1 - The role of checkpoint blockade after allogeneic stem cell transplantation in diseases other than Hodgkin's Lymphoma

AU - Holderried, Tobias A W

AU - Fraccaroli, Alessia

AU - Schumacher, Martin

AU - Heine, Annkristin

AU - Brossart, Peter

AU - Stelljes, Matthias

AU - Klobuch, Sebastian

AU - Kröger, Nicolaus

AU - Apostolova, Petya

AU - Finke, Jürgen

AU - Zeiser, Robert

AU - Heinicke, Thomas

AU - Bornhäuser, Martin

AU - von Bergwelt-Baildon, Michael

AU - Tischer, Johanna

AU - Wolf, Dominik

PY - 2019/10

Y1 - 2019/10

N2 - 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.

AB - 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.

U2 - 10.1038/s41409-019-0498-0

DO - 10.1038/s41409-019-0498-0

M3 - SCORING: Journal article

C2 - 30833743

VL - 54

SP - 1662

EP - 1667

JO - BONE MARROW TRANSPL

JF - BONE MARROW TRANSPL

SN - 0268-3369

IS - 10

ER -