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TISAGENLECLEUCEL IN PEDIATRIC AND YOUNG ADULT PATIENTS (PTS) WITH RELAPSED/REFRACTORY (R/R) B-CELL ACUTE LYMPHOBLASTIC LEUKEMIA (B-ALL): FINAL ANALYSES FROM THE ELIANA STUDY
Author(s): ,
Susana Rives
Affiliations:
Department of Pediatric Hematology – Oncology,Hospital Sant Joan de Déu Barcelona, and Institut de Recerca Sant Joan de Déu,Barcelona,Espagne;Department of Pediatric Hematology – Oncology,Hospital Sant Joan de Déu Barcelona, and Institut de Recerca Sant Joan de Déu,Barcelona,Spanien;Department of Pediatric Hematology – Oncology,Hospital Sant Joan de Déu Barcelona, and Institut de Recerca Sant Joan
,
Shannon L. Maude
Affiliations:
Division of Oncology,Center for Childhood Cancer Research and Cancer Immunotherapy Program, Children's Hospital of Philadelphia and Department of Pediatrics, Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania,Philadelphia, PA,États-unis;Division of Oncology,Center for Childhood Cancer Research and Cancer Immunotherapy Program, Children's Hospital of Philadelphia and De
,
Hidefumi Hiramatsu
Affiliations:
Department of Pediatrics,Graduate School of Medicine, Kyoto University,Kyoto,Japon;Department of Pediatrics,Graduate School of Medicine, Kyoto University,Kyoto,Japan;Department of Pediatrics,Graduate School of Medicine, Kyoto University,Kyoto,Giappone;Department of Pediatrics,Graduate School of Medicine, Kyoto University,Kyoto,Japan;Department of Pediatrics,Graduate School of Medicine, Kyoto Unive
,
Andre Baruchel
Affiliations:
University Hospital Robert Debré (APHP) and Université de Paris,Paris,France;University Hospital Robert Debré (APHP) and Université de Paris,Paris,Frankreich;University Hospital Robert Debré (APHP) and Université de Paris,Paris,Francia;University Hospital Robert Debré (APHP) and Université de Paris,Paris,France;University Hospital Robert Debré (APHP) and Université de Paris,Paris,Francia;Universit
,
Peter Bader
Affiliations:
Division of Stem Cell Transplantation and Immunology,Hospital for Children and Adolescents, University Hospital Frankfurt,Frankfurt,Allemagne;Division of Stem Cell Transplantation and Immunology,Hospital for Children and Adolescents, University Hospital Frankfurt,Frankfurt,Deutschland;Division of Stem Cell Transplantation and Immunology,Hospital for Children and Adolescents, University Hospital Fr
,
Henrique Bittencourt
Affiliations:
Department of Pediatrics, Faculty of Medicine,University of Montreal, and the Hematology Oncology Division and Charles-Bruneau Cancer Center, Centre Hospitalier Universitaire Sainte-Justine Research Centre,Montreal, QC,Canada;Department of Pediatrics, Faculty of Medicine,University of Montreal, and the Hematology Oncology Division and Charles-Bruneau Cancer Center, Centre Hospitalier Universitaire
,
Jochen Buechner
Affiliations:
Department of Pediatric Hematology and Oncology,Oslo University Hospital,Oslo,Norvège;Department of Pediatric Hematology and Oncology,Oslo University Hospital,Oslo,Norwegen;Department of Pediatric Hematology and Oncology,Oslo University Hospital,Oslo,Norvegia;Department of Pediatric Hematology and Oncology,Oslo University Hospital,Oslo,Norway;Department of Pediatric Hematology and Oncology,Oslo Un
,
Theodore Laetsch
Affiliations:
Division of Oncology,Center for Childhood Cancer Research and Cancer Immunotherapy Program, Children's Hospital of Philadelphia and Department of Pediatrics, Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania,Philadelphia, PA,États-unis;Division of Oncology,Center for Childhood Cancer Research and Cancer Immunotherapy Program, Children's Hospital of Philadelphia and De
,
Barbara De Moerloose
Affiliations:
Department of Pediatric Hematology-Oncology and Stem Cell Transplantation,Ghent University Hospital,Ghent,Belgique;Department of Pediatric Hematology-Oncology and Stem Cell Transplantation,Ghent University Hospital,Ghent,Belgien;Department of Pediatric Hematology-Oncology and Stem Cell Transplantation,Ghent University Hospital,Ghent,Belgio;Department of Pediatric Hematology-Oncology and Stem Cell
,
Muna Qayed
Affiliations:
Aflac Cancer and Blood Disorders Center,Emory University,Atlanta, GA,États-unis;Aflac Cancer and Blood Disorders Center,Emory University,Atlanta, GA,Vereinigte Staaten;Aflac Cancer and Blood Disorders Center,Emory University,Atlanta, GA,Stati Uniti;Aflac Cancer and Blood Disorders Center,Emory University,Atlanta, GA,United States;Aflac Cancer and Blood Disorders Center,Emory University,Atlanta, GA
,
Heather E. Stefanski
Affiliations:
National Bone Marrow Donor Program, Be the Match, Division of Pediatric Blood and Marrow Transplant,University of Minnesota,Minneapolis, MN,États-unis;National Bone Marrow Donor Program, Be the Match, Division of Pediatric Blood and Marrow Transplant,University of Minnesota,Minneapolis, MN,Vereinigte Staaten;National Bone Marrow Donor Program, Be the Match, Division of Pediatric Blood and Marrow T
,
Kara L. Davis
Affiliations:
Division of Hematology, Oncology and Stem Cell Transplant, Department of Pediatrics,Stanford University School of Medicine,Stanford, CA,États-unis;Division of Hematology, Oncology and Stem Cell Transplant, Department of Pediatrics,Stanford University School of Medicine,Stanford, CA,Vereinigte Staaten;Division of Hematology, Oncology and Stem Cell Transplant, Department of Pediatrics,Stanford Unive
,
Paul L. Martin
Affiliations:
Pediatric Transplant and Cellular Therapy,Duke University Medical Center,Durham, NC,États-unis;Pediatric Transplant and Cellular Therapy,Duke University Medical Center,Durham, NC,Vereinigte Staaten;Pediatric Transplant and Cellular Therapy,Duke University Medical Center,Durham, NC,Stati Uniti;Pediatric Transplant and Cellular Therapy,Duke University Medical Center,Durham, NC,United States;Pediatri
,
Eneida Nemecek
Affiliations:
Oregon Health and Science University,Portland, OR,États-unis;Oregon Health and Science University,Portland, OR,Vereinigte Staaten;Oregon Health and Science University,Portland, OR,Stati Uniti;Oregon Health and Science University,Portland, OR,United States;Oregon Health and Science University,Portland, OR,Estados Unidos;Oregon Health and Science University,Portland, OR,Verenigde Staten;Oregon Healt
,
Christina Peters
Affiliations:
Stem Cell Transplantation Unit,St. Anna Children's Hospital,Vienna,Autriche;Stem Cell Transplantation Unit,St. Anna Children's Hospital,Vienna,Österreich;Stem Cell Transplantation Unit,St. Anna Children's Hospital,Vienna,Austria;Stem Cell Transplantation Unit,St. Anna Children's Hospital,Vienna,Austria;Stem Cell Transplantation Unit,St. Anna Children's Hospital,Vienna,Austria;Stem Cell Transplanta
,
Gregory Yanik
Affiliations:
Department of Pediatrics,University of Michigan Medical Center,Ann Arbor, MI,États-unis;Department of Pediatrics,University of Michigan Medical Center,Ann Arbor, MI,Vereinigte Staaten;Department of Pediatrics,University of Michigan Medical Center,Ann Arbor, MI,Stati Uniti;Department of Pediatrics,University of Michigan Medical Center,Ann Arbor, MI,United States;Department of Pediatrics,University
,
Adriana Balduzzi
Affiliations:
Clinica Pediatrica Università degli Studi di Milano Bicocca, Fondazione MBBM,Ospedale San Gerardo,Monza,Italie;Clinica Pediatrica Università degli Studi di Milano Bicocca, Fondazione MBBM,Ospedale San Gerardo,Monza,Italien;Clinica Pediatrica Università degli Studi di Milano Bicocca, Fondazione MBBM,Ospedale San Gerardo,Monza,Italia;Clinica Pediatrica Università degli Studi di Milano Bicocca, Fonda
,
Nicolas Boissel
Affiliations:
Saint-Louis Hospital (APHP) and Université de Paris,Paris,France;Saint-Louis Hospital (APHP) and Université de Paris,Paris,Frankreich;Saint-Louis Hospital (APHP) and Université de Paris,Paris,Francia;Saint-Louis Hospital (APHP) and Université de Paris,Paris,France;Saint-Louis Hospital (APHP) and Université de Paris,Paris,Francia;Saint-Louis Hospital (APHP) and Université de Paris,Paris,Frankrijk;S
,
Seong Lin Khaw
Affiliations:
Children's Cancer Centre,Royal Children's Hospital and Murdoch Children's Research Institute,Parkville, VIC,Australie;Children's Cancer Centre,Royal Children's Hospital and Murdoch Children's Research Institute,Parkville, VIC,Australien;Children's Cancer Centre,Royal Children's Hospital and Murdoch Children's Research Institute,Parkville, VIC,Australia;Children's Cancer Centre,Royal Children's Hos
,
Joerg Krueger
Affiliations:
Division of Haematology/Oncology/Bone Marrow Transplantation, Department of Paediatrics,The Hospital for Sick Children,Toronto, ON,Canada;Division of Haematology/Oncology/Bone Marrow Transplantation, Department of Paediatrics,The Hospital for Sick Children,Toronto, ON,Kanada;Division of Haematology/Oncology/Bone Marrow Transplantation, Department of Paediatrics,The Hospital for Sick Children,Toron
,
John Levine
Affiliations:
Tisch Cancer Institute,Icahn School of Medicine at Mount Sinai,New York, NY,États-unis;Tisch Cancer Institute,Icahn School of Medicine at Mount Sinai,New York, NY,Vereinigte Staaten;Tisch Cancer Institute,Icahn School of Medicine at Mount Sinai,New York, NY,Stati Uniti;Tisch Cancer Institute,Icahn School of Medicine at Mount Sinai,New York, NY,United States;Tisch Cancer Institute,Icahn School of M
,
Stella Davies
Affiliations:
Cincinnati Children's Hospital Medical Center,Cincinnati, OH,États-unis;Cincinnati Children's Hospital Medical Center,Cincinnati, OH,Vereinigte Staaten;Cincinnati Children's Hospital Medical Center,Cincinnati, OH,Stati Uniti;Cincinnati Children's Hospital Medical Center,Cincinnati, OH,United States;Cincinnati Children's Hospital Medical Center,Cincinnati, OH,Estados Unidos;Cincinnati Children's Ho
,
Gary Douglas Myers
Affiliations:
Children's Mercy Hospital and Clinics,Kansas City, MO,États-unis;Children's Mercy Hospital and Clinics,Kansas City, MO,Vereinigte Staaten;Children's Mercy Hospital and Clinics,Kansas City, MO,Stati Uniti;Children's Mercy Hospital and Clinics,Kansas City, MO,United States;Children's Mercy Hospital and Clinics,Kansas City, MO,Estados Unidos;Children's Mercy Hospital and Clinics,Kansas City, MO,Veren
,
Adeline Yeo
Affiliations:
Novartis Pharmaceuticals Corporation,East Hanover, NJ,États-unis;Novartis Pharmaceuticals Corporation,East Hanover, NJ,Vereinigte Staaten;Novartis Pharmaceuticals Corporation,East Hanover, NJ,Stati Uniti;Novartis Pharmaceuticals Corporation,East Hanover, NJ,United States;Novartis Pharmaceuticals Corporation,East Hanover, NJ,Estados Unidos;Novartis Pharmaceuticals Corporation,East Hanover, NJ,Veren
,
Darragh O'Donovan
Affiliations:
Novartis Pharmaceuticals Corporation,Dublin,Irlande;Novartis Pharmaceuticals Corporation,Dublin,Irland;Novartis Pharmaceuticals Corporation,Dublin,Irlanda;Novartis Pharmaceuticals Corporation,Dublin,Ireland;Novartis Pharmaceuticals Corporation,Dublin,Irlanda;Novartis Pharmaceuticals Corporation,Dublin,Ierland;Novartis Pharmaceuticals Corporation,Dublin,Irlanda;Novartis Pharmaceuticals Corporation,
,
Roberto Ramos
Affiliations:
Novartis Pharmaceuticals Corporation,East Hanover, NJ,États-unis;Novartis Pharmaceuticals Corporation,East Hanover, NJ,Vereinigte Staaten;Novartis Pharmaceuticals Corporation,East Hanover, NJ,Stati Uniti;Novartis Pharmaceuticals Corporation,East Hanover, NJ,United States;Novartis Pharmaceuticals Corporation,East Hanover, NJ,Estados Unidos;Novartis Pharmaceuticals Corporation,East Hanover, NJ,Veren
,
Michael Pulsipher
Affiliations:
Division of Pediatric Hematology and Oncology,Intermountain Primary Children's Hospital, Huntsman Cancer Institute at the University of Utah,Salt Lake City, UT,États-unis;Division of Pediatric Hematology and Oncology,Intermountain Primary Children's Hospital, Huntsman Cancer Institute at the University of Utah,Salt Lake City, UT,Vereinigte Staaten;Division of Pediatric Hematology and Oncology,Inte
Stephan Grupp
Affiliations:
Division of Oncology,Center for Childhood Cancer Research and Cancer Immunotherapy Program, Children's Hospital of Philadelphia and Department of Pediatrics, Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania,Philadelphia, PA,États-unis;Division of Oncology,Center for Childhood Cancer Research and Cancer Immunotherapy Program, Children's Hospital of Philadelphia and De
(Abstract release date: 05/12/22) EHA Library. Rives S. 06/12/22; 356977; S112
Susana Rives
Susana Rives
Contributions
Abstract
Presentation during EHA2022: All Oral presentations will be presented between Friday, June 10 and Sunday, June 12 and will be accessible for on-demand viewing from Monday, June 20 until Monday, August 15, 2022 on the Congress platform.

Abstract: S112

Type: Oral Presentation

Session title: Novel insights into the treatment of ALL

Background

Pediatric and young adult pts with R/R B-ALL experience a treatment journey characterized by diminishing likelihood of cure and increasing morbidity. Tisagenlecleucel is an autologous CD19-directed chimeric antigen receptor (CAR) T-cell therapy approved for use in pediatric and young adults with B-ALL and adults with B-cell lymphomas. Tisagenlecleucel provided high rates of remission (>80%) in children and young adults with R/R B-ALL in ELIANA, with 62% of responders remaining relapse-free at 24 mo (Grupp et al, Blood, 2018). 

Aims
Here, we report the final efficacy and safety analyses in pts followed up to 5.9 years post-tisagenlecleucel infusion.

Methods

ELIANA (NCT02435849) was a pivotal, Phase II, open-label, multicenter, global study of tisagenlecleucel in pediatric and young adult pts with R/R B-ALL. Pts received a single infusion of tisagenlecleucel at 0.2-5.0×106 CAR+ viable T cells/kg body weight for pts ≤50 kg and 0.1-2.5×108 CAR+ viable T cells for pts >50 kg. Endpoints included overall remission rate (ORR) within 3 mo, relapse-free survival (RFS), duration of remission (DOR), overall survival (OS), persistence of B-cell aplasia, and short- and long-term safety events.

Results

Results: As of September 24, 2021, 97 pts were enrolled and 79 pts (81%) received tisagenlecleucel. Median time from infusion to data cutoff was 5.5 y; 64 pts had ≥5 y of follow-up. At study entry, the median age was 11 y (range, 3-24). Pts were heavily pretreated with a median of 3 prior lines of therapy (range, 1-8) and 61% had a history of prior stem cell transplant (SCT). ORR (complete remission [CR] or CR with incomplete hematologic recovery within 3 mo after infusion) was 82% (95% CI, 72-90). Among pts in remission (CR/CRi), the 5y RFS rate was 49% (95% CI, 34-62), and the median RFS was not reached (Figure, 46.8 mo when censoring for SCT; n=15). The median time to B-cell recovery was 38.6 mo (95% CI, 23-not reached) and the probability of B-cell aplasia at 6 mo and 12 mo was 83% (95% CI, 71-91) and 71% (95% CI, 57-82), respectively. Pts with B-cell recovery (<6 mo, n=10; 6-12 mo, n=4; >12 mo, n=7) experienced a 2y cumulative incidence of relapse of 25.2% (with SCT treated as a competing risk). Among all pts, the 5y EFS and OS rates were 42% (95%CI, 29-54) and 55% (95% CI, 43-66), respectively. There were no significant differences in any efficacy endpoint between pediatric (<18 y; n=65) and young adult (≥18 y; n=14) pts. No new or unexpected AEs were reported during long-term follow-up. Among pts in remission, the most commonly reported grade ≥3 AEs occurring >1 y post-infusion were infection (20%) and cytopenias (6%). Ten (14%) pts in remission experienced long-term cytopenias persisting for >1 y; however, none of these pts experienced cytopenias persisting for >5 y (median 2 y; range, 1.1-5y). Eighty-two percent of pts received IVIG any time post-infusion.

Conclusion

This >5 y follow-up study demonstrates continued durable efficacy of tisagenlecleucel without late adverse effects in heavily pretreated pediatric and young adult pts with R/R B-ALL. Tisagenlecleucel continues to be a potentially curative treatment option for pediatric and young adult patients with R/R B-ALL.

Keyword(s): Acute lymphoblastic leukemia, Pediatric, Relapsed acute lymphoblastic leukemia

Presentation during EHA2022: All Oral presentations will be presented between Friday, June 10 and Sunday, June 12 and will be accessible for on-demand viewing from Monday, June 20 until Monday, August 15, 2022 on the Congress platform.

Abstract: S112

Type: Oral Presentation

Session title: Novel insights into the treatment of ALL

Background

Pediatric and young adult pts with R/R B-ALL experience a treatment journey characterized by diminishing likelihood of cure and increasing morbidity. Tisagenlecleucel is an autologous CD19-directed chimeric antigen receptor (CAR) T-cell therapy approved for use in pediatric and young adults with B-ALL and adults with B-cell lymphomas. Tisagenlecleucel provided high rates of remission (>80%) in children and young adults with R/R B-ALL in ELIANA, with 62% of responders remaining relapse-free at 24 mo (Grupp et al, Blood, 2018). 

Aims
Here, we report the final efficacy and safety analyses in pts followed up to 5.9 years post-tisagenlecleucel infusion.

Methods

ELIANA (NCT02435849) was a pivotal, Phase II, open-label, multicenter, global study of tisagenlecleucel in pediatric and young adult pts with R/R B-ALL. Pts received a single infusion of tisagenlecleucel at 0.2-5.0×106 CAR+ viable T cells/kg body weight for pts ≤50 kg and 0.1-2.5×108 CAR+ viable T cells for pts >50 kg. Endpoints included overall remission rate (ORR) within 3 mo, relapse-free survival (RFS), duration of remission (DOR), overall survival (OS), persistence of B-cell aplasia, and short- and long-term safety events.

Results

Results: As of September 24, 2021, 97 pts were enrolled and 79 pts (81%) received tisagenlecleucel. Median time from infusion to data cutoff was 5.5 y; 64 pts had ≥5 y of follow-up. At study entry, the median age was 11 y (range, 3-24). Pts were heavily pretreated with a median of 3 prior lines of therapy (range, 1-8) and 61% had a history of prior stem cell transplant (SCT). ORR (complete remission [CR] or CR with incomplete hematologic recovery within 3 mo after infusion) was 82% (95% CI, 72-90). Among pts in remission (CR/CRi), the 5y RFS rate was 49% (95% CI, 34-62), and the median RFS was not reached (Figure, 46.8 mo when censoring for SCT; n=15). The median time to B-cell recovery was 38.6 mo (95% CI, 23-not reached) and the probability of B-cell aplasia at 6 mo and 12 mo was 83% (95% CI, 71-91) and 71% (95% CI, 57-82), respectively. Pts with B-cell recovery (<6 mo, n=10; 6-12 mo, n=4; >12 mo, n=7) experienced a 2y cumulative incidence of relapse of 25.2% (with SCT treated as a competing risk). Among all pts, the 5y EFS and OS rates were 42% (95%CI, 29-54) and 55% (95% CI, 43-66), respectively. There were no significant differences in any efficacy endpoint between pediatric (<18 y; n=65) and young adult (≥18 y; n=14) pts. No new or unexpected AEs were reported during long-term follow-up. Among pts in remission, the most commonly reported grade ≥3 AEs occurring >1 y post-infusion were infection (20%) and cytopenias (6%). Ten (14%) pts in remission experienced long-term cytopenias persisting for >1 y; however, none of these pts experienced cytopenias persisting for >5 y (median 2 y; range, 1.1-5y). Eighty-two percent of pts received IVIG any time post-infusion.

Conclusion

This >5 y follow-up study demonstrates continued durable efficacy of tisagenlecleucel without late adverse effects in heavily pretreated pediatric and young adult pts with R/R B-ALL. Tisagenlecleucel continues to be a potentially curative treatment option for pediatric and young adult patients with R/R B-ALL.

Keyword(s): Acute lymphoblastic leukemia, Pediatric, Relapsed acute lymphoblastic leukemia

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