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4950 Outcome of Patients with HTLV-1 Adult T-Cell Leukemia/Lymphoma (ATL) after Allogeneic SCT: Results of the EBMT LWP

Program: Oral and Poster Abstracts
Session: 732. Allogeneic Transplantation: Disease Response and Comparative Treatment Studies: Poster III
Hematology Disease Topics & Pathways:
Clinical Practice (Health Services and Quality), Lymphomas, T Cell lymphoma, Diseases, Aggressive lymphoma, Lymphoid Malignancies
Monday, December 9, 2024, 6:00 PM-8:00 PM

Patricia Lopez Pereira1*, Ali Bazarbachi, MD, PhD2, Ambroise Marçais, MD, PhD3*, Maud Ngoya4*, Irma Khvedelidze5*, Ben Carpenter, MD6*, Victoria Potter7*, Flore Sicre de Fontbrune, MD8*, Alina Daniela Tanase, md, phd9, Lucy Cook, MD, MBBS, PhD, BSc, MB10*, Francesca Kinsella11*, Emma Nicholson, MD12*, Annoek E. C. Broers, MD13*, Jennifer Clay Sr., MD, PhD14*, Hélène Labussière-Wallet, MD15*, Fabio Ciceri, MD16*, Bertram Glass, MD17*, Olivier Hermine, MD, PhD18 and Ana Maria Sureda Balari, MD, PhD19,20

1Clinical Hematology Department, Institut Català d’Oncologia, Hospital Duran i Reynals, IDIBELL, Barcelona, Spain
2Bone Marrow Transplantation Program, Department of Internal Medicine, American University of Beirut, Beirut, Lebanon
3Department of Hematology, Institut Imagine, Necker Hospital, Paris Descartes University, Paris, France
4European Society for Blood and Marrow Transplantation, Paris, France
5European Bone Marrow Transplantation Lymphoma Working Party, Paris, France
6University College London Hospitals NHS Foundation Trust, London, United Kingdom
7Dept. of Haematological Medicine, King's College Hospital NHS Foundation Trust, London, United Kingdom
8Hematology Department, Saint-Louis Hospital, Paris, France
9Institutul clinic fundeni, clădirea B, director medical, Bucharest, Romania
10Imperial College Healthcare NHS Trust, London, United Kingdom
11Birmingham Centre for Cellular Therapy and Transplant (BCCTT), Birmingham, United Kingdom
12Royal Marsden NHS Foundation Trust, London, United Kingdom
13Erasmus MC Cancer Institute, Rotterdam, Netherlands
14Yorkshire Blood & Marrow Transplant Program, Leeds, United Kingdom
15Hôpital Lyon Sud, Hospices Civils de Lyon, Pierre-Bénite, France
16Hematology and Bone Marrow Transplantation Unit, I.R.C.C.S. San Raffaele Scientific Institute, Milan, Italy
17Department of Hematology and Stem Cell Transplantation, Helios Klinikum Berlin-Buch, Berlin, Germany
18Hematology, Necker Hospital, Greater Paris University Hospitals (AP-HP), Paris, France
19Lymphoma Working Party, On behalf of the EBMT (European Group for Blood and Marrow Transplantation), Barcelona, Spain
20Clinical Hematology Department, Institut Català d’Oncologia-Hospitalet, IDIBELL, Barcelona, Spain

Introduction: HTLV-1 positive ATL is an uncommon aggressive malignancy with a dismal prognosis. Allogeneic hematopoietic stem cell transplantation (allo-SCT) is a potentially curative treatment modality for these patients, but most of them do not reach the procedure due to progressive chemoresistant disease, poor performance status or lack of suitable donor. The aim of this study was to report and analyze the outcome of ATL patients after allo-SCT, focusing on the influence of ATL subtype, type of transplantation, donor characteristics, stem cell source, conditioning intensity and transplant outcomes.

Methods: We conducted a retrospective review of patients diagnosed with ATL from the EBMT registry who underwent allo-SCT from January 2004 to December 2021. All patients were ≥ 18 years and had a histologic diagnosis of ATL with HTLV-1 positive serology and/or PCR. We included any donor type and bone marrow (BM) or peripheral blood stem cells (PBSC). Cord blood transplants were excluded. Outcomes of interest were 2-year overall survival (OS) and 2-year progression free survival (PFS), relapse incidence (RI), non-relapse mortality (NRM), acute and chronic graft versus host disease (aGVHD and cGVHD).

Results: Seventy-three patients were included. Median age was 45 (range 26-67) years and 52% of patients were female. ATL subtype was acute (19%), chronic (6%), lymphomatous (73%) and smoldering (2%). Median time from diagnosis to allo-SCT was 8 months (range 3-93). Disease status at allo-SCT was complete remission in 69%, partial remission 21% and active/progressive disease 10%. Sixty-four (64%) patients had received 1 line of therapy before allo-SCT and 36% received 2 or more lines. Karnofsky performance status was ≥ 90% in 74% of the patients. Donor type was mismatched relative in 40%, matched family donor 33%, and unrelated 27% of the cases. Thirty-two (32%) of donors were haploidentical. Ninety-one (91%) of donors were HLTV negative. Graft source was PBSC in 89% and BM in 11% of the cases. Most of the patients (n=55, 75%) underwent a reduced intensity conditioning (RIC) regimen. The most common regimen was Busulfan-Fludarabine-Thiotepa in 19% of cases. Thirty percent (30%) of patients received total body irradiation (TBI). GvHD prophylaxis contained calcineurin inhibitors plus mycophenolate mofetil combinations in 43 (59%) patients. Twenty-eight (38%) patients received post-transplant cyclophosphamide (PTCy).

Median follow up of the cohort was 3.9 years (range 3-6.1). Two-year-OS was 49% (95% CI 37-60) and 2-year-PFS was 43% (95% CI 31-54). NRM and RI were 7% (95% CI 3-15%) and 35% (95% CI 38-61%) at two years, respectively. The cumulative incidence of grade II-IV acute GvHD was 7% (95% CI 3-15%) at 100 days. At two years, the cumulative incidence of chronic GvHD was 38% (95% CI 26-49%). At the time of the analysis 41 patients had died. Causes of death were progression in 26 (67%), HSCT related in 9 (23%), and other causes in 4 (10%) of the cases. In univariate analysis no statistically significant differences in NRM, aGVHD II-IV and cGVHD were identified according to conditioning regimen, number of prior lines of therapy, disease status, Karnofsky score or ATL subtype. OS and PFS were higher in patients in CR at allo-SCT (56% versus 33%, p=0.002 and 50% versus 27%, p=0.01, respectively). RI was lower in this group (44% versus 63%, p=0.01). This finding was confirmed on multivariate analysis. Non-CR was associated with lower PFS (HR 2.93, 95%CI 11.23-6.99; p=0.01) and OS (HR 4.12, 95%CI 1.65-10.29; p=0.002) and higher RI (HR 2.66, 95%CI 1.05-6.75; p=0.04). Haploidentical donor was associated with better OS (HR 0.46, 95%CI 0.23-0.94; p=0.03). Also, having received 2 or more lines of therapy prior to allo-SCT was associated to higher cGVHD (HR 4.52, 95%CI 1.76-11.63; p=0.002) and extensive cGVHD (HR 5.34, 95%CI 1.41-20.23; p=0.01).

Conclusions: Allo-SCT consolidation is a feasible consolidation strategy for ATL patients, especially for those reaching CR prior to the procedure. In a cohort with predominantly ATL lymphoma, the ATL subtype did not impact the outcome of transplant and disease progression remains the main cause of death.

Disclosures: Bazarbachi: Jansen: Honoraria, Research Funding; Amgen: Honoraria; Caribou: Honoraria; Pfizer: Research Funding; Biologix: Research Funding; Takeda: Honoraria; Roche: Honoraria, Research Funding. Carpenter: Bluebird Biotech: Honoraria; Vertex Pharmaceuticals Incorporated: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Sicre de Fontbrune: Sobi: Honoraria, Research Funding; Samsung: Honoraria, Research Funding; Alexion, AstraZeneca Rare Disease: Honoraria, Research Funding; Novartis: Honoraria, Research Funding. Nicholson: Kite/Gilead: Honoraria, Research Funding; Novartis: Honoraria; BMS/Celgene: Honoraria; Autolus: Membership on an entity's Board of Directors or advisory committees. Ciceri: ExCellThera: Membership on an entity's Board of Directors or advisory committees. Glass: Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees; Miltenyi: Consultancy; Abbvie: Consultancy; Sobie: Consultancy; JAZZ: Honoraria. Hermine: Alexion: Research Funding; BMS: Research Funding; Inatherys: Consultancy, Current equity holder in publicly-traded company, Patents & Royalties, Research Funding; Roche: Research Funding; AB Science: Consultancy, Current equity holder in publicly-traded company, Patents & Royalties, Research Funding; MSD Avenir: Research Funding. Sureda Balari: BMS/Celgene: Consultancy; Novartis: Consultancy; Janssen: Consultancy; Gilead: Consultancy; Takeda: Consultancy; Sanofi: Consultancy.

*signifies non-member of ASH