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1437 Similar Outcome of Adolescents and Young Adults (AYA) and Older Adults with Newly Diagnosed Acute Lymphoblastic Leukemia (ALL) without Philadelphia Chromosome (Ph-) Included in the Pethema LAL-2019 Trial

Program: Oral and Poster Abstracts
Session: 613. Acute Lymphoblastic Leukemias: Therapies Excluding Allogeneic Transplantation: Poster I
Hematology Disease Topics & Pathways:
Clinical Practice (Health Services and Quality)
Saturday, December 7, 2024, 5:30 PM-7:30 PM

Anna Torrent, MD1*, Mireia Morgades2*, Susana Barrera3*, Jordi Ribera2*, Beatriz Soriano4*, Pau Montesinos, PhD, MD5,6*, Eulàlia Genescà2*, José González-Campos, M.D.7*, Pere Barba, MD8, Jordi Esteve, MD, PhD9,10, Marta Sitges11*, Maria Paz Queipo De Llano12*, Carmen Botella13*, Clara Maluquer Artigal, MD14*, Irene García-Cadenas, MD15*, Marisa Calabuig16*, Alberto Hernández-Sánchez17*, Laura Torres, MD18*, Isabel Granada, MD2*, Jesus Maria Hernandez Rivas, MD19,20, Alberto Orfao, MD, PhD4* and Josep-Maria Ribera, MD, PhD21,22

1Hematology department, Institut Català D'oncologia-Hospital Germans Trias I Pujol. Josep Carrera, Badalona, Spain
2ICO-Hospital Germans Trias i Pujol, Institut de Recerca contra la Leucèmia Josep Carreras (IJC), Universitat Autònoma de Barcelona, Badalona, Spain
3Translational and Clinical Research Program, Cancer Research Center (IBMCC, CSIC – University of Salamanca); Cytometry Service, NUCLEUS; Department of Medicine, University of Salamanca (Universidad de Salamanca), Salamanca, Spain. IBSAL (Salamanca, Spain), Salamanca, Spain
4Cancer Research Center (IBMCC-CSIC/USAL-IBSAL), Cytometry Service (NUCLEUS) and Department of Medicine, University of Salamanca, Salamanca, Spain
5Hematology, Hospital Universitari I Politécnic La Fe and Programa Español de Tratamientos en Hematología (PETHEMA) Group, Valencia, Spain
6Department of Hematology, Instituto de Investigación Sanitaria La Fe, Valencia, Spain
7Hematology Department, Hospital Universitario Virgen del Rocío, Sevilla, Spain, Sevilla, Spain
8Vall d’Hebron Institute of Oncology (VHIO), Department of Hematology, University Hospital Vall d'Hebron, Universitat Autònoma of Barcelona (UAB), Barcelona, Spain
9Fundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi i Sunyer (FRCB-IDIBAPS), Barcelona, Spain
10Hematology Department, Hospital Clínic de Barcelona, Barcelona, Spain
11Hematology Department, Institut Català d`Oncologia, Girona, ESP
12Hematology Department Hospital Universitario Virgen de la Victoria, Málaga, Spain, Malaga, ESP
13Hospital General Universitario de Alicante, Alicante, Spain
14Hematology Department. Institut Català d’Oncologia, Hospital Duran i Reynals. Institut d’Investigació Biomèdica de Bellvitge (IDIBELL), L’Hospitalet de Llobregat, Barcelona, Spain
15Hematology Service, Hospital Santa Creu i Sant Pau, Barcelona, Spain
16Hematology department, Hospital Clínico de Valencia. Instituto de Investigación Sanitaria INCLIVA de Valencia, Valencia, Spain., Valencia, Spain
17Departmente of Hematology, University Hospital Salamanca, Barcelona, Spain
18Hematology department, Hospital Universitario la Fe de Valencia, Valencia, Spain., Valencia, Spain
19Servicio de Hematología, Hospital Universita­rio de Salamanca, Universidad de Salamanca, Salamanca, Spain
20Department of Medicine, University of Salamanca, Institute of Biomedical Research of Salamanca (IBSAL), University of Salamanca – Cancer Research Center of Salamanca (IBMCC, USAL-CSIG), Salamanca, Spain
21Ico-Hospital Universitari Germans Trias Y Pujol, Badalona, Barcelona, ESP
22Josep Carreras Leukemia Research Institute, Badalona, Barcelona, Spain., Badalona, Spain

Introduction. The treatment of Ph-negative ALL is based on pediatric-inspired protocols that include allogeneic hematopoietic stem cell transplantation (alloHSCT) based on post-induction/consolidation measurable residual disease (MRD) and genetic characteristics. The PETHEMA LAL-2019 protocol (NCT 04179929) includes patients (pts) aged 18-60 yrs with Ph- ALL. The indication for alloHSCT is based on the post-induction MRD level (≥0.01%) and/or the presence of adverse genetic factors (for B-cell ALL the presence of near/low hypodiploidy <40 chromosomes and >35 yrs, KMT2A translocations, homozygote deletions/mutations of TP53, or IKZF1 and CDKN2A/B deletions. For T-cell ALL the absence of NOTCH1/FBXW7 mutations together with RAS/PTEN mutations as well as ETP-ALL). Preliminary results in AYA (18-40 years) were analyzed and their outcome was compared with those of the older adults (41-60 yrs).

Methods. A centralized immunophenotypic (next-generation cytofluorometry) and genetic (FISH, SNP arrays and NGS) study was carried out in parallel with the induction-1 (Ind-1) treatment (vincristine, prednisone, PEG-asparaginase and daunorubicin). Pts without adverse genetic risk (AGR) and MRD <0.01% received 3 cycles of early consolidation (HD-MTX, HD ARAC and PEG-asparaginase) and reinduction. If MRD was <0.001% at that point, pts received 3 cycles of delayed consolidation and maintenance therapy. The remaining pts were assigned to alloHSCT. Refractory pts or those with MRD ≥0.01% after Ind-1 received a 2nd induction cycle (Ind-2) (FLAG-Ida or Inotuzumab after amendment). Pts with early T cell precursor (ETP) ALL received differentiated treatment (induction with FLAG-Ida, 3 cycles of early consolidation (HD-MTX, HD ARAC and PEG-asparaginase) and alloHSCT.

Results. Between December 2019 and March 2024, 476 valid pts were included, 245 (51%) AYA. Median age 27 (18-40 y), 150 (61%) males, CNS infiltration 19/170 (11%), leukocytes 18x10e9/L (0.4-740), B-cell precursor ALL 178 (73%), T-ALL 67 (27%, ETP 18/67, 27%), standard genetic risk (SGR) 110/187 (59%), AGR 77/187 (41%). The CR rate after Ind-1 was 83%, and after Ind-1+Ind-2 was 94%. There were two deaths in Ind-1 and five in Ind-2. Overall 74/122 (61%) showed MRD<0.01% after Ind-1. Sixty-five pts were assigned to chemotherapy (CT) (RD<0.01% after I-1 and SGR [n=41] or RD<0.01% and genetic risk (GR) not available [n=24]). The remaining were assigned to alloHSCT (AGR only [n=20], RD post Ind-1 ≥0.01% regardless of GR [n= 49] or no CR after Ind-1 [n=25]). The probability of OS at 3 yrs for AYA was 65% (95%CI: 55%-73%), vs. 63% (51%-72%) for those at 41-60 yrs (p=0.676). The cumulative incidence of relapse (CIR) at 3-years in AYA was 39% (28%-49%) vs. 43% (29%-55%) for those aged 41-60 yrs (p=0.676). The subgroup of AYA with MRD <0.01% and SGR had a probability of OS at 3-years of 84% (61%-94%), significantly higher than the remaining groups, with no significant differences between them.

Conclusions. The preliminary results in ALL pts included in the LAL-2019 protocol are comparable to those of other pediatric-inspired protocols. No differences in OS and CIR were observed when compared AYA (18-40 yrs) with adults aged 41-60 yrs. The subgroup of low-risk AYA pts had excellent survival without need for alloHSCT.

Disclosures: Torrent: Pfizer: Honoraria; Incyte: Honoraria; Kite: Honoraria; Amgen: Honoraria. Montesinos: Syndax: Consultancy; Servier: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: research support, Research Funding, Speakers Bureau; Novartis: Consultancy, Research Funding, Speakers Bureau; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: research support, Research Funding, Speakers Bureau; Daiichi Sankyo, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: research support, Research Funding, Speakers Bureau; Jazzpharma: Consultancy, Research Funding, Speakers Bureau; Astellas: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: research support, Speakers Bureau; Glycomimetics: Consultancy; Janssen: Membership on an entity's Board of Directors or advisory committees, Other: research support, Speakers Bureau; Kura Oncology: Consultancy; Pfizer: Consultancy, Research Funding, Speakers Bureau. Barba: Autolus: Consultancy; Kite-Gielead: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Pfizer: Honoraria; Incyte: Honoraria; BMS: Honoraria. Hernandez Rivas: Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; GlaxoSmithKline: Consultancy, Honoraria; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Ribera: Incyte: Consultancy; Pfizer: Consultancy; Bristol Myers Squibb: Consultancy; Novartis: Consultancy; Takeda: Consultancy; Amgen: Research Funding.

*signifies non-member of ASH