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79 Personalized Risk-Profiling for Acute Leukemia Patients Undergoing Haploidentical Allogeneic Hematopoietic Stem Cell Transplantation: A Study on Behalf of the Acute Leukemia Working Party of the EBMT

Program: Oral and Poster Abstracts
Type: Oral
Session: 732. Clinical Allogeneic Transplantation: Results I
Hematology Disease Topics & Pathways:
Leukemia, ALL, AML, Biological, Adult, Diseases, Therapies, Technology and Procedures, Lymphoid Malignancies, Study Population, Myeloid Malignancies, Clinically relevant, transplantation
Saturday, December 5, 2020: 8:30 AM

Joshua A Fein, MD1,2, Roni Shouval, MD, PhD3, Myriam Labopin, MD4,5*, Fabio Ciceri, MD6*, Emanuele Angelucci, MD7, Didier Blaise, MD8, Johanna Tischer9*, William Arcese, MD, PhD10, Yener Koc, MD11, Benedetto Bruno, MD12*, Jose L. Diez-Martin, MD, PhD13, Stella Santarone, MD14, Simona Sica, MD, PhD15*, Jurjen Versluis16*, Mohamad Mohty, MD, PhD17,18 and Arnon Nagler, MD19,20

1Department of Internal Medicine, UConn Health, West Hartford, CT
2Department of Internal Medicine, UConn Health, Farmington, CT
3Adult Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
4Sorbonne Universités, UPMC Univ Paris 06, INSERM, Centre de Recherche Saint-Antoine (CRSA), Paris, France
5EBMT ALWP, Paris, France
6San Raffaele Telethon Institute for Gene Therapy (SR-TIGET), IRCCS San Raffaele Scientific Institute, Milan, Italy
7Hematology and Transplant Center, IRCCS Ospedale Policlinico San Martino, Genova, Italy
8Institut Paoli Calmettes, Marseille, France
9Department of Internal Medicine III, University Hospital of Munich-Grosshadern, Ludwig-Maximilians University, Munich, Germany, Munich, Germany
10Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy
11Medicana International, Istanbul, TUR
12SSCVD Trapianto di Cellule Staminali, AOU Città della Salute e della Scienza di Torino, Torino, Italy
13Department of Hematology, Hospital General Universitario Gregorio Marañón, Madrid, Spain
14Department of Oncology Hematology, Pescara Hospital, Pescara, Italy
15Fondazione Policlinico A. Gemelli IRCCS, Roma, Italy; Istituto di Ematologia, Università Cattolica del Sacro Cuore, Roma, Italy, Roma, Italy
16Erasmus University Medical Center Cancer Institute, Rotterdam, Rotterdam, Netherlands
17Hospital Saint-Antoine, Paris University UPMC, INSERM U938, Paris, France
18EBMT, Acute Leukemia Working Party, Paris, France
19EBMT, Acute Leukemia Working Party office, Paris, France
20Division of Hematology, Sheba Medical Center, Tel Hashomer, Israel

Background: Prediction of patient outcomes following allogeneic hematopoietic stem cell transplantation (HSCT) remains a tenacious problem. An important limitation of current prediction models is the heterogeneity in outcome even among similar cases. We introduce a novel approach to individualizing estimates of leukemia-free survival (LFS) in acute leukemia patients undergoing haploidentical (haplo) HSCT.

Methods: Data were obtained from the registry of the European Society for Blood and Marrow Transplantation for all cases of haplo HSCT for acute leukemia performed between 2011 and 2017. Patients receiving ex-vivo T-cell depleted grafts were excluded. Acute myeloid leukemia patients were classified by clinical disease ontogeny (de novo vs. secondary), cytogenetics, and FLT3-ITD/NPM1mut status; acute lymphoblastic leukemia patients by disease status and the presence of the Philadelphia chromosome. Common patient and transplantation parameters including recipient age, Karnofsky performance status (KPS), time from diagnosis to transplantation, conditioning and graft-versus-host disease (GvHD) prophylaxis were included. Data were split into training and geographic validation sets.

Results: A total of 2,001 patients was included in the training set and another 270 in the validation cohort. In the training set, the median age was 50 years; 68% of patients were in complete remission, and 69% had a KPS ≥ 90; 87% received post-transplant cyclophosphamide and 13% antithymocyte globulin for GvHD prophylaxis. To provide the clinician insight on outcomes of similar patients, we developed a descriptive tool to visually explore outcomes of cases with comparable features. We next generated 50 random survival forest models for the prediction of 1-year LFS. In contrast to single point-estimates, the ensemble of 50 models generates a prediction interval accounting for predictive uncertainty. There was heterogeneity of variable importance between models, with either disease status or KPS leading in all models (Figure A). The model was well calibrated (Figure B); the median c-statistic was 0.64 on the validation set. An online interface presents the individual outcomes of the fifteen patients most similar to the index case, the prediction interval, and a visualization of all 50 survival forest predictions. Predictions for a sample patient are shown in Figure (C).

Conclusions: We present the first system for individualized prediction of leukemia-free survival following T-cell replete haplo transplantation. A key, novel component of the model, distinguishing it from standard risk scores, is that it provides a measure of predictive certainty. This is essential for judging the robustness of prediction. Our approach is applicable to other clinical settings and can be used for designing risk-guided interventions and for informing patients and clinicians.

Disclosures: Labopin: Jazz Pharmaceuticals: Honoraria. Blaise: Jazz Pharmaceuticals: Honoraria. Sica: F. Hoffmann-La Roche Ltd: Other: All authors received support for third-party writing assistance, furnished by Scott Battle, PhD, provided by F. Hoffmann-La Roche, Basel, Switzerland., Research Funding. Mohty: Stemline: Consultancy, Honoraria, Research Funding, Speakers Bureau; Takeda: Consultancy, Honoraria, Research Funding, Speakers Bureau; Jazz Pharmaceuticals: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Sanofi: Consultancy, Honoraria, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau; BMS: Consultancy, Honoraria, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Research Funding, Speakers Bureau; GSK: Consultancy, Honoraria, Research Funding, Speakers Bureau.

*signifies non-member of ASH