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1902 Outcome of Adults with Relapsed T-Cell Acute Lymphoblastic Leukemia (T-ALL) Included in Minimal Residual Disease (MRD)-Oriented Trials

Program: Oral and Poster Abstracts
Session: 612. Acute Lymphoblastic Leukemia: Clinical Studies: Poster II
Hematology Disease Topics & Pathways:
Leukemia, ALL, Adult, Diseases, Lymphoid Malignancies, Study Population
Sunday, December 6, 2020, 7:00 AM-3:30 PM

Josep-Maria Ribera1, Eduardo Cerello Chapchap, MD2*, Mireia Morgades, M.Prob.S1*, Eulàlia Genescà, PhD1*, Cristina Gil3*, Irene García-Cadenas4*, Pere Barba, MD, PhD5*, José González-Campos, MD6*, Anna Torrent1*, Teresa Bernal del Castillo, MD, PhD7*, Maria Paz Queipo De Llano, MD8*, María-Luz Amigo, MD9*, Mar Tormo, MD10, Rosa Coll, MD11*, Ferran Vall-Llovera, MD12*, Jordi Ribera, PhD1*, Maria Jose Sanchez, MD13*, Beatriz Soria, MD14*, Antonia Cladera15*, María Teresa Artola, MD16*, Antoni Garcia-Guiñon, MD17*, Alberto Giménez Conca, MD18*, Lourdes Amador Barciela, MD19*, Juana Ciudad, PhD20* and Alberto Orfao, MD, PhD20

1Hematology Department, ICO-Hospital Germans Trias i Pujol. Josep Carreras Research Institute. Universitat Autònoma de Barcelona, Badalona, Spain
2Hospital Israelita Albert Einstein, São Paulo, Brazil
3Hematology Department, Hospital General Universitario de Alicante, Alicante, Spain
4Hematology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
5Hematology Department, Hospital Universitari Vall d'Hebron. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain
6Hematology Department, Hospital Universitario Virgen del Rocio. Instituto de Biomedicina de Sevilla (IBIS)/CSIC/CIBERONC. Universidad de Sevilla, Sevilla, Spain
7Hospital Universitario Central Asturias, ISPA, IUOPA, Oviedo, Spain
8Hospital Universitario Virgen de la Victoria, Málaga, Spain
9Hematology Department, Hospital General Universitario Morales Meseguer, Murcia, Spain
10Hospital Clínico Universitario de Valencia, Valencia, Spain
11Hematology Department, ICO - Hospital Doctor Josep Trueta, Girona, Spain
12Hematology Department, Hospital Mutua de Terrassa, Terrassa, Spain
13Hematology Department, Hospital Universitario Lucus Augusti, Lugo, Spain
14Hematology Department, Hospital Universitario de Canarias, Santa Cruz de Tenerife, Spain
15Hematology Department, Hospital Universitario Son Llàtzer, Palma de Mallorca, Spain
16Hematology Department, Hospital Universitario de Donostia, Donostia, Spain
17Hospital Universitari Arnau de Vilanova, Lleida, Spain
18Section of Hematology, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
19Hematology Department, Complejo Hospitalario Pontevedra, Pontevedra, Spain
20IBSAL, IBMCC, Centro de Investigación del Cáncer, CIBERONC, Universidad de Salamanca-CSIC, Hospital Universitario, Salamanca, Spain

Introduction and objective. Despite a high complete remission (CR) rate obtained with frontline therapy most adults with T-ALL eventually relapse. Although promising therapies are emerging, salvage options for T-ALL are currently limited. Little is known about outcome of patients (pts) with relapsed T-ALL (R T-ALL) treated with contemporary MRD-oriented trials. Our goal was to analyze the outcome of pts with R T-ALL included in two successive MRD-oriented trials (ALL-AR-03 and ALL-HR-11) from the Spanish PETHEMA Group.

Methods. Retrospective study of R T-ALL adults diagnosed between 2003 and 2019 and included in the protocols ALL-AR-03 (NCT00853008) and ALL-HR-11 (NCT01540812). The clinical characteristics at baseline and at relapse, salvage therapies and outcomes (CR and OS) were analyzed and a study of prognostic factors for OS was performed.


Forty-nine patients were identified (ALL-AR-03 [n=27], ALL-HR-11 [n=22]). Median age (range) at diagnosis was 29 (16-58) yrs, 38 males (78%), CNS involvement 6 (12%), mediastinal mass 30 (61%), WBC count 40.8 x109/L (0.6-351.0), early T-cell precursor 11 (23%), pre-T 8 (16%), cortical 16 (33%), mature 9 (18%), T unspecified 5 (10%). Post-induction-1 MRD level ≥0.1%: 14/42 (33%), ≥0.01%: 17/39 (44%). Nine pts (18%) required 2nd induction therapy (resistant disease after induction-1 [n=5], MRD≥0.1% after induction-1 [n=4]). Allogeneic HSCT in CR1: 8 pts. Interval CR1-relapse: 11.2 [0.1-36.7] months. Relapse was located in BM (n=20, 41%), BM+extramedullary (n=16, 33%) and extramedullary (n=13, 26%). CNS at relapse was involved in 18 pts (37%, isolated in 8 cases).

Median number of rescue lineages was 2 (range 1-5). The most frequent first salvage schedules were FLAG-Ida (n=24, 49%), HyperCVAD (n=8, 16%) and nelarabine (n=4, 8%) (other schedules in 13 pts). Second CR was attained in 21/48 pts (44%). The patients with poor morphologic and/or poor MRD response after Induction-1 in first line therapy (n=9) did not respond to first salvage therapy (0/9 vs. 21/39, p=0.003). AlloHSCT was performed in 19 pts (15 in CR2) (HLA-identical sibling: 9, URD: 9, haploidentical: 1, myeloablative conditioning: 16). Thirty-nine pts died (progression: 27, toxicity of rescue regimens: 7, TRM: 5) and 9/10 alive patients were submitted to HSCT (the remaining is on rescue therapy). Median OS (95%CI) was 6.1 (4.9-7.2) months, 5yr OS probability 21% (9%-33%) (Figure 1). By multivariable analysis, only the CR after first salvage regimen emerged as favorable prognostic factor for OS (HR 3.110, 95%CI: 1.579-6.124) (Figure 2).

Conclusion. This study shows poor outcome of adults with R T-ALL, with CR to first salvage therapy of 44% and a median OS of 6 months. Poor early response to first line therapy correlated with poor response to salvage-1. The only independent predictor for better survival was CR to first salvage regimen. This study highlights the unmet need for novel effective therapies for T-ALL.

Supported in part by grant 2017 SGR288 (GRC) Generalitat de Catalunya and “La Caixa” Foundation; ISCIII (PI19/01828), co-funded by ERDF/ESF, "A way to make Europe"/"Investing in your future".

Disclosures: Ribera: Pfizer, Amgen, Ariad, Novartis: Consultancy, Speakers Bureau; Pfizer, Amgen: Research Funding. Barba: Amgen, Celgene, Gilead, Jazz Pharmaceuticals, Novartis, Pfizer, Shire: Consultancy; Amgen, Celgene, Novartis, Pfizer: Speakers Bureau. Tormo: Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria; MSD: Honoraria; Daiichi Sankyo: Honoraria; Servier: Honoraria; Roche: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees. Sanchez: Abbvie: Other: travel grants; Amgem: Other: travel grants; Janssen: Other: travel grants; Celgene: Other: travel grants; Roche: Other: travel grants. Giménez Conca: AbbVie: Honoraria, Speakers Bureau.

*signifies non-member of ASH