Relapse. 2y-OS 14% Cell-based therapy in CR 2y-OS 55% X. Poiré et al. 2

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1 Sequential administration of 5-azacytidine (AZA) and donor lymphocyte infusion (DLI) for patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) in relapse after allogeneic stem cell transplantation (SCT): an interim analysis from the Belgian Hematological Society (BHS). Xavier Poiré, Carlos Graux, Aurélie Ory, Jacques Jamart, Frédéric Baron, Hélène Schoemans, Philippe Lewalle, Ann De Becker, Dries Deeren, Zwi Berneman, Tessa Kerre, Pierre Zachée, Dominik Selleslag, Yves Beguin.

2 X. Poiré et al. 2 Relapse 2y-OS 14% Cell-based therapy in CR 2y-OS 55% Schmid et al. Blood 2012

3 X. Poiré et al. 3 Azacytidine after allo-sct Craddock et al. Haematologica 2016

4 X. Poiré et al. 4 Azacytidine inreases GvL Craddock et al. BBMT 2016 Goodyear et al. Blood 2012

5 X. Poiré et al. 5 Inclusion/Exclusion criteria INCLUSION CRITERA Age > 18 yo AML in CR or MDS with less than 10% blasts at SCT Related or unrelated donor (10 or 9/10) Myeloablative or reduced-intensity conditioning regimen Cytologic, immunophenotypic, cytogenetic or molecular relapse Immunosuppressive therapy should be withdrawed before inclusion EXCLUSION CRITERA Relapse with more than 30% blasts at inclusion Extramedullary relapse ECOG > 2 Acute and chronic GvHD Uncontrolled infection Severe cardiac, renal, pulmonary, neurologic or hepatic impairment

6 X. Poiré et al. 6 Treatment schedule DLI Dose Cycle 2 Cycle 4 Cycle 6 Sibling 5x10 7 CD3+/kg Unrelated 1x10 7 CD3+/kg 5x10 7 CD3+/kg 5x10 7 CD3+/kg 1x10 8 CD3+/kg 1x10 8 CD3+/kg CR : 2 additionnal AZA cycles END PR/SD : continue AZA till progression

7 X. Poiré et al. 7 Patients characteristics Patients characteristics (N=49) Median age at inclusion (range) 56 year-old (17-73) Median follow-up 163 days Median time from SCT to relapse (range) 312 days ( ) Diagnosis at SCT, N (%) AML 29 (59%) MDS 20 (41%) saml/t-aml, N(%) 19 (39%) Disease status at SCT, N (%) CR1 37 (76%) CR2 2 (4%) >CR2 3 (6%) MDS with less 10% blasts 7 (14%) Karyotype at diagnosis (ELN 2017) Intermediate Adverse Unkown Gender, N (%) Male Female 22 (47%) 25 (53%) 2 26 (53%) 23 (47%)

8 X. Poiré et al. 8 Patients characteristics (cont d) Conditioning regimen, N (%) MAC RIC Donor type, N (%) Sibling Unrelated Patients characteristics (N=49) 11 (22%) 38 (78%) 15 (31%) 34 (69%) Clonal evolution at relapse 10 (20%) Median blasts at relapse (range) 10% (0-28,8) Relapse while still on IS, N (%) 26 (53%) Median time of IS withdrawal (range) 2 days (1-39) Median number of AZA cycles (range) 3 (1-10) Median number of DLI (range) 1 (1-3)

9 X. Poiré et al. 9 Patients flow 15 6 AZA 5 CR 1 PR 2 deaths (infection/relapse) 3 still in CR ongoing AZA 3 exclusions 4 SD 1 ongoing AZA 3 deaths from PD 52 screening 49 analyzed 2 Ongoing AZA 5 PD 3 agvhd 4 deaths 1 CR after salvage 2 infections 32 early drop off 21 PD 3 patient 3 donor

10 X. Poiré et al. 10 Overall Survival Median survival 7.7 months

11 X. Poiré et al. 11 Grade 3/4 toxicities and GvHD Toxicity N (%) at least once Anemia 5 (10%) Neutropenia 12 (24%) Thrombocytopenia 10 (20%) Febrile neutropenia 13 (27%) Fever 3 (6%) Dyspnea 2 (4%) Effusions 2 (4%) Septic chock 2 (4%) Hospitalization 33 (67%) GvHD N agvhd grade II-IV 3 cgvhd 7

12 X. Poiré et al. 12 Conclusions This AZA-DLI schedule results only in a few CR. CR/PR patients : Median marrow blasts 7% at relapse 4 adverse KT and 2 intermediate median time from SCT to relapse = 89 days Most patients dropped off the study for disease progression (N=21) Very few cases of GvHD Hematological toxicities were significant This AZA-DLI schedule might be more appropriate as a prophylactic therapy after allo- SCT in high-risk patients Correlative study : Lymphocytes subsets : Pr Zagury, Dr Le Bouanec, Pr Bensussan, St-Louis (INSERM U976) Assocation with different time points during the therapy

13 X. Poiré et al. 13 Aknowledgements Carlos Graux, MD, PhD Celgene (Veronique Libotte, Frédéric Mauroy) Yves Beguin, MD, PhD Aurélie Ory Jacques Jamart All the BHS Transplant committee members All the data managers All the participating patients and their family