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965 Second Infusion of CAR T-Cells in Patients with Relapsed /Refractory B-Cell Acute Lymphoblastic Leukemia: Results from a Gocart Coalition Analysis on Behalf of the PDWP, ALWP, and Ctiwp of the EBMT

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, Adult, ALL, Lymphoid Leukemias, Clinical Research, Pediatric, Therapy sequence, Diseases, Treatment Considerations, Real-world evidence, Lymphoid Malignancies, Registries, Study Population, Human
Monday, December 9, 2024: 5:30 PM

Susana Rives1,2*, Giorgio Ottaviano3*, Nuria Martínez-Cibrián, MD4*, Shatha Y. Farhan, MD5, Sowjanya Vuyyala, MBBS6,7, Jacques-Emmanuel Galimard, PhD8*, Eva Michel9*, Fizza Imran9*, Nazaret Sánchez-Sierra, MD10*, Richard Mitchell, MBBS11*, Stephan Mielke, MD12, Andishe Attarbaschi, MD13*, Soeren Lykke Petersen, MD, MSc14*, Samppa Ryhanen Sr., MD, PhD15, Wolfgang Andreas Bethge, MD16*, David Beauvais, MD17*, Tsila Zuckerman, MD18, Antonio Pérez-Martínez19,20,21,22*, Krzysztof Kalwak, MD, PhD23*, Fabio Ciceri, MD24*, Annalisa Ruggeri, MD, PhD25*, Julio Delgado, MD, PhD26,27*, Sebastian Giebel, MD, PhD28*, Adriana Balduzzi, MD29,30, Anna Alonso-Saladrigues, MD1,2,31* and Valentin Ortiz-Maldonado, MD, PhD, MSc26

1Department of Pediatric Hematology and Oncology, Hospital Sant Joan de Déu, Barcelona, Spain
2Institut de Recerca Sant Joan de Déu, Barcelona, Spain
3Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy
4Hematology Department, Hospital Clínic Barcelona, Barcelona, Spain, Barcelona, Spain
5Department of Stem Cell Transplant and Cellular Therapy, Henry Ford Hospital, Detroit, MI
6Hematology and Oncology, Mayo Clinic, Rochester, MN
7Hematology and Oncology, Mayo Clinic, Rochester
8EBMT Paris Office, Hôpital Saint Antoine, Paris, France
9EBMT Paris Study Unit, Saint Antoine Hospital, INSERM UMR-S 938, Sorbonne University, Paris, France
10Department of Pediatric Hematology and Oncology, Hospital Sant Joan de Déu de Barcelona, Barcelona, Spain
11Kids Cancer Centre, Sydney Children`s Hospital, Randwick, Australia
12Department of Cellular Therapy and Allogeneic Stem Cell Transplantation (CAST), Karolinska Comprehensive Cancer Center and ATMP Center, Karolinska Institutet and University Hospital, Stockholm, Sweden
13Department of Pediatric Hematology and Oncology, St. Anna Kinderspital, Vienna, Austria
14Department of Hematology, Copenhagen University Hospital, Copenhagen, Denmark
15Hospital For Children and Adolescent, Helsinki University Central Hospital, Helsinki, Finland
16Department of Internal Medicine II, Hematology, Oncology, Clinical Immunology and Rheumatology, University Hospital Tuebingen, Tübingen, Germany
17Hematology Department., CHRU Lille, Lille, FRA
18Department of Hematology and Bone Marrow Transplantation, Rambam Health Care Campus, Moshav Ein Ayalla, Israel
19Department of Pediatric Hemato-Oncology, University Hospital La Paz, Madrid, Spain
20CIBERER-ISCIII,, Madrid, Spain
21Pediatric Department, Autónoma University of Madrid, Madrid, Spain
22IdiPAZ-CNIO Pediatric Onco-Hematology Clinical Research Uni, Madrid, Spain
23Department of Pediatric Hematology, Oncology and BMT, Wroclaw Medical University, Wroclaw, Poland
24Hematology and Bone Marrow Transplantation Unit, I.R.C.C.S. San Raffaele Scientific Institute, Milan, Italy
25Hematology and Bone Marrow Transplant Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
26Hospital Clínic de Barcelona, Barcelona, Spain
27Instituto de Investigaciones Biomédicas August Pi i Sunyer (IDIBAPS), Barcelona, Spain
28Department of Hematology and Bone Marrow Transplantation, Maria Sklodowska-Curie Institute of Oncology, Gliwice, Poland
29Fondazione IRCCS San Gerardo dei Tintori, Pediatric Hematopoietic Stem Cell Transplant Unit, Monza, Italy
30University of Milano-Bicocca, School of Medicine and Surgery, Monza, Italy
31University of Barcelona, Barcelona, Spain

Background:

The prognosis of patients (pts) with relapsed or refractory B ALL (r/r B-ALL) treated with CAR T-cells and receive a 2nd CART infusion is unknown. Few reports with limited numbers of patients suggest that 2nd CART infusion is feasible with questionable efficacy. This GoCART coalition registry study aimed at compiling data to investigate the indications, efficacy, and toxicity of CART2 infusion in pts with r/r B-ALL.

Methods:

This is a multicenter, retrospective registry study that included pediatric and adult patients with r/r B-ALL who received autologous CD19-targeted CAR T-cell therapy (CART1) and subsequently were treated with a second administration of CD19 and/or CD22-targeted CAR-T cell therapy (CART2) from 2017 to 2023. Baseline features, prior stem cell transplant (SCT), indications for CART2 and outcomes were collected. Relapse incidence (RI) was defined as overt recurrence, non-relapse mortality (NRM) as death without relapse occurrence, leukemia free survival (LFS) as being alive without occurrence of relapse and overall survival (OS) as being alive. RI and NRM were estimated using cumulative incidence function and OS and LFS Kaplan-Meier estimation.

Results:

Out of 345 pts who received CART1, 39 (2y cumulative incidence of second CART: 12.4% (95%CI: 8.8-16.6)) received CART2. Reasons for CART2 were overt relapse (n= 26; 66.7%), molecular relapse by measurable residual disease (MRD+) (n=5; 12.8%), and B-cell recovery (BCR) in the absence of relapse (n=8; 20.5%). Seventeen pts (43.6%) were female and median age at CART2 infusion was 19 yrs (range: 6.9-67.1), including 19 children and 20 adults. 74.4% of the pts had received a prior SCT, 25 pts (64%) before CART1, 2 (5.1%) only between CART1 and CART2, and 2 (5.1%) before CART1 and between CART1 and CART2. Among the 31 pts who received CART2 for relapse, this was CD19+ in 24 (92.3%), CD19- in 2 (7.7%), and unknown in 5. CART1 products were varnimcabtagene autoleucel (ARI-0001) (23), tisagenlecleucel (13), brexucabtagene autoleucel (1), and other experimental (2). All CART2 products targeted CD19 except 2 (1 CD22 and 1 dual CD19-CD22).

Median time between CART1 and CART2 was 11.0 months. For patients who received CART2 for BCR, median time between CART1 and CART2 was shorter than for those who received it for relapse: 2.4 (IQR: 2.3-3.3) months vs. 12.4 (IQR:6.4-19.3) months. Regarding leukemic burden at the time of CART2 infusion, 19 pts (48.8%) were in overt relapse (14/19 with extramedullary disease, including 7 in CNS), 12 (30.1%) were in complete remission (CR) MRD+ and 8 (20.5%) CR MRD-.

With a median follow-up time of 2.3 yrs [95% CI: 1.2-3.4], the 2-yr OS and LFS after CART2 were 47.1% [95% CI: 27.8-64.3] and 39.9% [95% CI: 24-55.3], respectively. 2-yr RI was 54.5% (95% CI: 36.5-69.4) and NRM was 5.6% (95% CI 1-16.8). 2-yr OS, LFS and RI for pts in CR at CART2 infusion irrespective to MRD were 76.1%, 63.3% and 25.6% while for those not in CR these outcomes were 17.7%, 15% and 85%, respectively (p= 0.007, 0.006 and 0.002). 2-yr LFS (71.4% [95% CI 25.8-92]) and RI (0%) was significantly better for pts receiving CART2 for BCR than in those who received it for relapse (31.6% [15.6-48.9] and 68.4% [46.7-82.8]; p= 0.036, p=0.002).

Conclusion:

This is a large registry study describing indications and outcome of CART2 in patients with r/r B-ALL. At 2-yrs after CART2, the LFS was of 39.9% and for patients receiving CART2 due to B-cell recovery was of 71.4%. These results show that CART2 is associated with low NRM and might be a bridge to SCT or other additional therapies. Updated results with data about subsequent therapies after CART2 will be presented at ASH meeting.

Disclosures: Rives: Kite/ Gilead: Honoraria; Pfizer: Honoraria; Clinigen: Honoraria; Amgen: Honoraria; Autolus: Other: Data monitoring committee; Celgene/ Bristol Myers Squibb: Honoraria; Servier: Honoraria; Novartis: Honoraria, Other: DMSB in trial sponsored by Novartis. Martínez-Cibrián: Kite/Gilead: Honoraria, Other: Travel Expenses. Mielke: Kiadis Pharma: Research Funding; Celgene/BMS: Speakers Bureau; Immunicum/Mendes: Membership on an entity's Board of Directors or advisory committees; Janssen: Speakers Bureau; KITE/GILEAD: Research Funding, Speakers Bureau; Miltenyi: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Speakers Bureau; Pfizer: Speakers Bureau; Scientify Research: Current equity holder in private company; SWECARNET: Membership on an entity's Board of Directors or advisory committees. Petersen: Novartis, Kite/Gilead: Speakers Bureau. Ryhanen: Medac and Jazz Pharmaceuticals: Other: travel grant; AMGEN: Consultancy. Beauvais: Kite/Gilead: Honoraria, Speakers Bureau. Kalwak: Medac: Speakers Bureau; Novartis: Speakers Bureau; Pierre Fabre: Other: Travel Grant, Speakers Bureau; Merck: Speakers Bureau. Ciceri: ExCellThera: Membership on an entity's Board of Directors or advisory committees. Giebel: Equity Ownership (Private company): Research Funding; Immunicum/Mendes: Membership on an entity's Board of Directors or advisory committees; Miltenyi: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene/BMS, Janssen, Pfizer: Speakers Bureau; Gilead/Kite: Research Funding, Speakers Bureau; Kiadis Pharma, The Netherlands: Research Funding. Balduzzi: Neovii: Speakers Bureau; Medac: Speakers Bureau; Amgen: Speakers Bureau; Novartis: Speakers Bureau. Ortiz-Maldonado: Miltenyi: Honoraria; Pfizer: Honoraria; Kite/Gilead: Honoraria, Other: Travel grants; Janssen: Honoraria, Other: Travel grants; Celgene-BMS: Honoraria, Other: Travel grants; Hospital Clínic de Barcelona: Current Employment; Novartis: Honoraria.

OffLabel Disclosure: varmincabtagene autoleucel is approved under hospital exemption in adult patients with relapsed or refractory B-ALL. In children is off-label.

*signifies non-member of ASH