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707 Donor Lymphocyte Infusions for the Treatment of Relapsed Non-Hodgkin Lymphoma Following Allogeneic Stem Cell Transplantation: A LWP-EBMT Study

Program: Oral and Poster Abstracts
Type: Oral
Session: 723. Clinical Allogeneic and Autologous Transplantation: Late Complications and Approaches to Disease Recurrence: Therapy of Post-Transplantation Relapse
Hematology Disease Topics & Pathways:
Diseases, Biological, Adult, Therapies, Non-Hodgkin Lymphoma, Study Population, Lymphoid Malignancies, Clinically relevant, transplantation
Monday, December 3, 2018: 11:30 AM
Grand Hall B (Manchester Grand Hyatt San Diego)

Stephen Robinson, MBBS, PhD, BSc1*, Ariane Boumendil, PhD2*, Hervé Finel3*, Irma Khvedelidze4*, Edward Kanfer, MBBS, PhD, BSc5*, Karl Peggs, MBBChir6*, Sabine Furst, MD7*, Ron Ram8*, Waf Marijt, MD9, Elisabeth Vandenberghe, MD, PhD10*, Boris Afanasiev, MD11*, Gerald Wulf, MD12*, Yves Chalandon, MD, PhD13, Johan Maertens14*, Anna Tsoulkani15*, Michel Schaap, MD, PhD16*, Dietrich W. Beelen17, Gunhan Gurman18*, Jürgen Finke, MD19, Sebastian Wittnebel20*, Paolo Di Bartolomeo, MD21, Johanna Tischer22*, Paolo Corradini, MD23, Dolores Caballero, MD24, Maria A V Marzolini25*, Claire Burney1*, Giorgio La Nasa, MD26*, Victoria Potter27*, Jörg Thomas Bittenbring, MD28*, Nathalie Fegueux29*, Nicolaus Kroeger, MD30, Norbert Schmitz, MD31*, Peter Dreger32 and Silvia Montoto, MD33

1University Hospital's Bristol, Bristol, United Kingdom
2EBMT Lymphoma Working Party Paris Office, Paris, France
3Lymphoma Working Party, EBMT, Paris, France
4EBMT LWP Paris Office, Hopital Saint-Antoine, Paris, France
5Hammersmith Hospital, London, United Kingdom
6Stem Cell Transplant, University College London Hospital, London, United Kingdom
7Institut Paoli Calmettes, Marseille, France
8Tel Aviv Medical Center and Sacker Faculty Of Medicine, Tel Aviv, ISR
9Leiden University Hospital, Leiden, Netherlands
10St James Hospital and Trinity College Dublin, Dublin, IRL
11First State Pavlov Medical University of St. Petersburg, Raisa Gorbacheva Memorial Research Institute for Paediatric Oncology, Hematology, and Transplantation, St Petersburg, Russia, St.Petersburg, Russia
12Clinics of Hematology and Medical Oncology, University Medicine Göttingen, Göttingen, Germany
13Division of Hematology, Geneva University Hospital and Faculty of Medicine, Geneva, Switzerland
14University Hospital Gasthuisberg, Leuven, Belgium
15Nottingham University, Nottingham, United Kingdom
16Radboud University Medical Centre, Nijmegen, Netherlands
17Department of Bone Marrow Transplantation, University Hospital Essen, Essen, Germany
18Department of Hematology, Ankara University School of Medicine, Ankara, Turkey
19Department of Hematology, Oncology and Stem Cell Transplantation, Faculty of Medicine, University of Freiburg, Freiburg, Germany
20Institut Jules Bordet, Brussels, Belgium
21"Santo Spirito" Civic Hospital, Department of Hematology, Transfusion Medicine and Biotechnology, Pescara, Italy
22University Hospital of Munich-LMU, Munich, Germany
23Hematology Division and Hemato-Oncology Department, University of Milan, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
24Hematology Department, Hospital Clínico Universitario de Salamanca (CAUSA/IBSAL), Salamanca, Spain
25UCL Cancer Institute, London, United Kingdom
26Department of Medical Sciences, University of Cagliari, Cagliari, Italy
27King's College Hospital NHS Foundation Trust, London, United Kingdom
28Department of Hematology, Oncology, Rheumatology and Clinical Immunology, Saarland University Medical Center, Homburg, Germany
29Department of Hematology, CHU Lapeyronie, Montpellier, France
30Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
31Univesitaetsklinikum Muenster, Muenster, Germany
32Dept. Medicine V, University Hospital Heidelberg, Heidelberg, Germany
33Centre for Haemato-Oncology, Barts Cancer Institute, Queen Mary University of London, London, United Kingdom

Introduction

Relapse of non-Hodgkin lymphoma (NHL) following allogeneic stem cell transplantation (alloSCT) is a common occurrence associated with a poor outcome with limited treatment options. Donor lymphocyte infusions (DLI) are commonly employed in this setting in an attempt to exploit the allogeneic graft versus lymphoma (GVL) effect to induce remissions. There is however a paucity of data describing the efficacy of DLIs in inducing remissions in NHL subtypes and the risk of subsequently developing graft versus host disease (GVHD). We report here the largest series of patients with NHL receiving DLI for relapse after alloSCT.

Methods

Patients relapsing after an alloSCT for NHL and receiving DLI were identified on the EBMT database. Centres were invited to contribute additional data. 118 patients [follicular lymphoma (FL) n=28, diffuse large B cell lymphoma (DLBCL) n=28, T cell lymphoma (TCL) n=52 and mantle cell lymphoma (MCL) n=10] from 39 centres who received DLI as the only treatment for relapse were identified. Patients receiving DLI in combination with other therapy were excluded from this analysis. The median age at alloSCT was 50 (range 18-73) years. There were 81 male and 37 female patients who underwent an alloSCT with reduced intensity (RIC) (n=90) or myeloablative conditioning (MAC) (n=28) at a median of 2.4 (range 0.3-26.3) years from diagnosis. Allogeneic cells were provided from matched sibling (n=63), unrelated (n=47) or mismatched family (n=8) donors and 85 patients received either ATG/ALG or CAMPATH as part of GVHD prophylaxis. The median time from alloSCT to relapse was 3.8 months (range 18 days-67 months).

Results

Patients received a median of 1 (range 1-19) DLI at a median starting dose of 1.5 x106 CD3/kg (range 0.01-120x106 CD3/kg) at a median of 152 days (range 18-2136) post alloSCT. The median last dose of DLI was 10x106/kg (range 0.1-180x106/kg) given at a median of 353 days (range 41-2725) post alloSCT. The median time from relapse to the first DLI was 35 days (range 0-168). Acute GVHD and chronic GVHD prior to DLI was reported in 29% and 14% of patients, respectively. Of 93 evaluable patients 47 (51%) patients achieved a complete remission, 10 (11%) a partial remission, 13 (14%) stable disease and 23 (25%) had progressive disease following DLI. The median duration of response was 36 months (range 1-168). When analysed according to histology the overall response rate (ORR) (CR+PR) for FL was 84% (CR 68%), DLBCL 41% (32% CR), TCL 54% (46% CR) and MCL 86% (CR 71%). The median duration of responses for FL, DLBCL, TCL and MCL were 30 (range 2-150), 38 (4-76), 37 (range 1-168) and 50 months (13-116) respectively. With a median follow up of 77 months after the 1st DLI 36 (31%) patients remain in complete remission, 29 (25%) without any further therapy. 37 (35%) went on to receive additional antilymphoma therapy after the DLI. Of 17 patients with FL achieving a CR post DLI 12 (71%) remain in remission without further therapy at a median of 78 (9-158) months after DLI. Of 18 patients with TCL that achieved a CR with DLI, 15 (83%) remain in remission without further therapy at a median of 95 (range 42-161) months after DLI. Following the DLI 43 (36%) patients developed aGVHD (6 grade I, 13 grade II, 11 grade III, 9 grade IV, 4 grade unknown) and 33 (28%) developed cGVHD (11 limited, 20 extensive, 2 unknown). Following the first DLI the cumulative incidence of relapse was 31% (CI 22-41) at 4 years and of NRM 28% (CI 20-37). The 4-year PFS after 1st DLI was 39% (CI 30-50) and the OS, 44% (CI 35-54).

Conclusions

DLI induce significant rates of disease response in patients with NHL relapsing after alloSCT providing clear proof of principle of the allogeneic GVL effect. The rates of response are most impressive in FL and MCL. The majority of patients with TCL and FL that achieve a CR post DLI remain in remission with long term follow up. Acute and chronic GVHD is a significant complication of DLI.

Disclosures: Robinson: Sandoz: Speakers Bureau; Gilead: Honoraria, Speakers Bureau; Takeda: Consultancy, Honoraria, Speakers Bureau; Roche: Consultancy, Honoraria, Speakers Bureau. Chalandon: Roche: Membership on an entity's Board of Directors or advisory committees, Other: Travel costs. Beelen: Medac: Consultancy, Other: Travel Support. Finke: Novartis: Consultancy, Honoraria, Other: travel grants, Research Funding; Neovii: Consultancy, Honoraria, Other: travel grants, Research Funding; Medac: Consultancy, Honoraria, Other: travel grants, Research Funding; Riemser: Consultancy, Honoraria, Research Funding. Tischer: Jazz Pharmaceuticals: Other: Jazz Advisory Board. Corradini: Amgen: Honoraria, Other: Advisory Board & Lecturer; Novartis: Honoraria, Other: Advisory Board & Lecturer; Abbvie: Honoraria, Other: Advisory Board & Lecturer; Sandoz: Other: Advisory Board; Sanofi: Honoraria, Other: Advisory Board & Lecturer; Gilead: Honoraria, Other: Advisory Board & Lecturer; Takeda: Honoraria, Other: Advisory Board & Lecturer; Roche: Honoraria, Other: Advisory Board & Lecturer; Janssen: Honoraria, Other: Lecturer; Celgene: Honoraria, Other: Advisory Board & Lecturer.

*signifies non-member of ASH