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962 Prognostic Impact of the Genetic Risk at Baseline Associated to the MRD Clearance in Adult Patients with Newly Diagnosed Acute Lymphoblastic Leukemia. Preliminary Results of Pethema LAL19 Trial

Program: Oral and Poster Abstracts
Type: Oral
Session: 613. Acute Lymphoblastic Leukemias: Therapies Excluding Allogeneic Transplantation: Risk Stratification and CAR-T Therapies
Hematology Disease Topics & Pathways:
Research, Clinical Practice (Health Services and Quality), Clinical Research, Therapy sequence, Real-world evidence, Treatment Considerations
Monday, December 9, 2024: 4:45 PM

Anna Torrent, MD1,2*, Mireia Morgades3*, Beatriz Soriano4*, Jordi Ribera3*, Susana Barrera5*, Pau Montesinos, PhD, MD6*, Eulàlia Genescà3*, José González-Campos, M.D.7*, Pere Barba, MD8,9, Jordi Esteve, MD, PhD10,11, Marta Sitges12*, Maria Paz Queipo De Llano13*, Carmen Botella14*, Clara Maluquer Artigal, MD15*, Irene García-Cadenas, MD16*, Marisa Calabuig17*, Alberto Hernández Sánchez, MD5*, Laura Torres, MD18*, Isabel Granada, MD3*, Jesus Maria Hernandez Rivas, MD19, Alberto Orfao, MD, PhD4* and Josep-Maria Ribera, MD, PhD20,21

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

Introduction. Young and middle-aged adults with ALL (18-60 years) who receive a pediatric-inspired chemotherapy (CHT) regimen for treatment of Ph-neg ALL do not appear to require an alloHSCT if they had a negative MRD after induction therapy. It is not clear if the genetic risk at baseline associated with this MRD approach, would allow identifying with more accuracy those patients who will receive CHT or alloHSCT. The aim of the prospective LAL19 trial from the Spanish PETHEMA Group was to evaluate the outcomes of pts assigned to a differentiated post-induction therapy (chemotherapy or alloHSCT) according to MRD levels (assessed by 8-color, centrally-performed flow cytometry at the end of induction –week 5- and consolidation therapy –week 17-) and genetic features at diagnosis.

Patients and methods. Pts with HR genetic features and/or those without good MRD response (MRD≥0.01% at end of induction-1 (ind-1) and ≥0.001% at end of consolidation) were assigned to receive an alloHSCT after consolidation. Pts with genetic HR features included for B-ALL: KMT2A translocation, near/low hypodiploidy (<40 chromosomes) and <35 years old, mutations/deletions of TP53 in homozygosis, or the presence of IKZF1 and CDKN2A/B mutations concomitantly, and all T-ALL except those with NOTCH1/FBXW7 isolated mutations. This analysis excluded pts with ETP-ALL because they received a different protocol.

Results. From December 2019 to March 2024, 452 pts with ALL were included. Median age was 40 (range 18-60) yrs, 57% male, 82% B-ALL, 40% HR genetic features. After Ind-1 83% (257/309) achieved CR, and it increased to 93% (286/309) after ind-2. After Ind-1+Ind-2, pts with CR and negative MRD (<0.01%) were 162/250 (65%): SR 30% (75/250), HR 19% (48/250) and unavailable genetics 16% (39/250). Overall, 179 pts (61%) were assigned to alloHSCT. The median follow-up was 12.1 (range 0.12-50.04) months. The 2-year probability of OS and CIR (95%CI) for the whole series were 66% (59% to 73%) and 35% (28% to 42%) respectively. For pts with neg-MRD/SR, neg-MRD/HR, pos-MRD and those without CR the 2-year probability of OS (95%CI) were 86% (71% to 94%), 59% (36% to 77%), 56% (41% to 69%) and 55% (33% to 73%), respectively (p=0.001). The 2-year CIR (95%CI) for pts with neg-MRD/SR, neg-MRD/HR, pos-MRD and those without CR were 15% (7% to 26%), 42% (24% to 59%), 49% (34% to 62%) and 54% (24% to 77%), respectively (p=0.001). A subgroup of patients with negative MRD (<0.001%) at day 14 and 35 have a very good prognosis with a 2-year probability OS of 87% (56% to 97%). Compared with the prior HR ALL11 trial (in which the decision to transplant or not was made based only in the MRD level) the 2-year CIR was reduced from 37% (29% to 44%) to 19% (10% to 28%) in patients allocated to CHT.

Conclusions. In adult ALL patients the inclusion of the genetic risk together with the MRD response to allocate the post-consolidation therapy, allow a better selection of patients who will receive CHT (neg-MRD and SR genetics at baseline). Patients with poor genetic risk at baseline had similar OS and CIR than those pts who were refractory, suggesting that the genetic risk highly relevant for prognosis assessment in adult ALL.

Disclosures: Torrent: Incyte: Honoraria; Kite: Honoraria; Pfizer: Honoraria; Amgen: Honoraria. Montesinos: 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; Janssen: Membership on an entity's Board of Directors or advisory committees, Other: research support, Speakers Bureau; Astellas: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: research support, Speakers Bureau; Servier: 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; Pfizer: Consultancy, Research Funding, Speakers Bureau; Novartis: Consultancy, Research Funding, Speakers Bureau; Kura Oncology: Consultancy; Syndax: Consultancy; Glycomimetics: Consultancy. 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; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Consultancy, Honoraria; 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