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EFFICACY AND SAFETY OF DARATUMUMAB IN PEDIATRIC AND YOUNG ADULT PATIENTS WITH RELAPSED/REFRACTORY T-CELL ACUTE LYMPHOBLASTIC LEUKEMIA OR LYMPHOBLASTIC LYMPHOMA: RESULTS FROM PHASE 2 DELPHINUS STUDY
Author(s): ,
Ajay Vora
Affiliations:
Department of Haematology,Great Ormond Street Hospital for Children,London,Royaume-uni;Department of Haematology,Great Ormond Street Hospital for Children,London,Vereinigtes Königreich;Department of Haematology,Great Ormond Street Hospital for Children,London,Regno Unito;Department of Haematology,Great Ormond Street Hospital for Children,London,United Kingdom;Department of Haematology,Great Ormond
,
Teena Bhatla
Affiliations:
Department of Pediatrics,Children's Hospital of New Jersey at Newark Beth Israel Medical Center,Newark, NJ,États-unis;Department of Pediatrics,Children's Hospital of New Jersey at Newark Beth Israel Medical Center,Newark, NJ,Vereinigte Staaten;Department of Pediatrics,Children's Hospital of New Jersey at Newark Beth Israel Medical Center,Newark, NJ,Stati Uniti;Department of Pediatrics,Children's H
,
David Teachey
Affiliations:
Division of Oncology,Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania,Philadelphia, PA,États-unis;Division of Oncology,Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania,Philadelphia, PA,Vereinigte Staaten;Division of Oncology,Center for
,
Francisco Bautista
Affiliations:
Princess Máxima Center for Pediatric Oncology,Utrecht,Pays-bas;Princess Máxima Center for Pediatric Oncology,Utrecht,Niederlande;Princess Máxima Center for Pediatric Oncology,Utrecht,Paesi Bassi;Princess Máxima Center for Pediatric Oncology,Utrecht,Netherland;Princess Máxima Center for Pediatric Oncology,Utrecht,Países Bajos;Princess Máxima Center for Pediatric Oncology,Utrecht,Nederland;Princess
,
John Moppett
Affiliations:
Paediatric Haematology,Bristol Royal Hospital for Children,Bristol,Royaume-uni;Paediatric Haematology,Bristol Royal Hospital for Children,Bristol,Vereinigtes Königreich;Paediatric Haematology,Bristol Royal Hospital for Children,Bristol,Regno Unito;Paediatric Haematology,Bristol Royal Hospital for Children,Bristol,United Kingdom;Paediatric Haematology,Bristol Royal Hospital for Children,Bristol,Rei
,
Pablo Velasco Puyó
Affiliations:
Servicio de Oncología y Hematología Pediátricas, Vall d'Hebron Hospital,Barcelona,Espagne;Servicio de Oncología y Hematología Pediátricas, Vall d'Hebron Hospital,Barcelona,Spanien;Servicio de Oncología y Hematología Pediátricas, Vall d'Hebron Hospital,Barcelona,Spagna;Servicio de Oncología y Hematología Pediátricas, Vall d'Hebron Hospital,Barcelona,Spain;Servicio de Oncología y Hematología Pediátr
,
Concetta Micalizzi
Affiliations:
Clinical Experimental Haematology Unit,IRCCS Istituto Giannina Gaslini,Genova,Italie;Clinical Experimental Haematology Unit,IRCCS Istituto Giannina Gaslini,Genova,Italien;Clinical Experimental Haematology Unit,IRCCS Istituto Giannina Gaslini,Genova,Italia;Clinical Experimental Haematology Unit,IRCCS Istituto Giannina Gaslini,Genova,Italy;Clinical Experimental Haematology Unit,IRCCS Istituto Gianni
,
Claudia Rossig
Affiliations:
University Children's Hospital Münster,Münster,Allemagne;University Children's Hospital Münster,Münster,Deutschland;University Children's Hospital Münster,Münster,Germania;University Children's Hospital Münster,Münster,Germany;University Children's Hospital Münster,Münster,Alemania;University Children's Hospital Münster,Münster,Duitsland;University Children's Hospital Münster,Münster,Alemanha;Univ
,
Neerav Shukla
Affiliations:
Department of Pediatrics,Memorial Sloan Kettering Cancer Center,New York, NY,États-unis;Department of Pediatrics,Memorial Sloan Kettering Cancer Center,New York, NY,Vereinigte Staaten;Department of Pediatrics,Memorial Sloan Kettering Cancer Center,New York, NY,Stati Uniti;Department of Pediatrics,Memorial Sloan Kettering Cancer Center,New York, NY,United States;Department of Pediatrics,Memorial Sl
,
Gil Gilad
Affiliations:
Department of Pediatric Hematology-Oncology,Schneider Children's Medical Center of Israel,Petach Tikva,Israël;Department of Pediatric Hematology-Oncology,Schneider Children's Medical Center of Israel,Petach Tikva,Israel;Department of Pediatric Hematology-Oncology,Schneider Children's Medical Center of Israel,Petach Tikva,Israele;Department of Pediatric Hematology-Oncology,Schneider Children's Medi
,
Franco Locatelli
Affiliations:
Department of Pediatric Hematology and Oncology,IRCCS Ospedale Pediatrico Bambino Gesù, Sapienza University of Rome,Rome,Italie;Department of Pediatric Hematology and Oncology,IRCCS Ospedale Pediatrico Bambino Gesù, Sapienza University of Rome,Rome,Italien;Department of Pediatric Hematology and Oncology,IRCCS Ospedale Pediatrico Bambino Gesù, Sapienza University of Rome,Rome,Italia;Department of P
,
André Baruchel
Affiliations:
Pediatric Hematology and Immunology Department,Robert Debré University Hospital (APHP and Université de Paris),Paris,France;Pediatric Hematology and Immunology Department,Robert Debré University Hospital (APHP and Université de Paris),Paris,Frankreich;Pediatric Hematology and Immunology Department,Robert Debré University Hospital (APHP and Université de Paris),Paris,Francia;Pediatric Hematology an
,
C. Michel Zwaan
Affiliations:
Princess Máxima Center for Pediatric Oncology,Utrecht,Pays-bas;Princess Máxima Center for Pediatric Oncology,Utrecht,Niederlande;Princess Máxima Center for Pediatric Oncology,Utrecht,Paesi Bassi;Princess Máxima Center for Pediatric Oncology,Utrecht,Netherland;Princess Máxima Center for Pediatric Oncology,Utrecht,Países Bajos;Princess Máxima Center for Pediatric Oncology,Utrecht,Nederland;Princess
,
Elizabeth A. Raetz
Affiliations:
New York University Langone Medical Center,New York, NY,États-unis;New York University Langone Medical Center,New York, NY,Vereinigte Staaten;New York University Langone Medical Center,New York, NY,Stati Uniti;New York University Langone Medical Center,New York, NY,United States;New York University Langone Medical Center,New York, NY,Estados Unidos;New York University Langone Medical Center,New Yo
,
Nibedita Bandyopadhyay
Affiliations:
Janssen Research & Development, LLC,Raritan, NJ,États-unis;Janssen Research & Development, LLC,Raritan, NJ,Vereinigte Staaten;Janssen Research & Development, LLC,Raritan, NJ,Stati Uniti;Janssen Research & Development, LLC,Raritan, NJ,United States;Janssen Research & Development, LLC,Raritan, NJ,Estados Unidos;Janssen Research & Development, LLC,Rarit
,
Lorena Lopez Solano
Affiliations:
Janssen Research & Development, LLC,Spring House, PA,États-unis;Janssen Research & Development, LLC,Spring House, PA,Vereinigte Staaten;Janssen Research & Development, LLC,Spring House, PA,Stati Uniti;Janssen Research & Development, LLC,Spring House, PA,United States;Janssen Research & Development, LLC,Spring House, PA,Estados Unidos;Janssen Research &am
,
Robyn M. Dennis
Affiliations:
Janssen Research & Development, LLC,Spring House, PA,États-unis;Janssen Research & Development, LLC,Spring House, PA,Vereinigte Staaten;Janssen Research & Development, LLC,Spring House, PA,Stati Uniti;Janssen Research & Development, LLC,Spring House, PA,United States;Janssen Research & Development, LLC,Spring House, PA,Estados Unidos;Janssen Research &am
,
Robin Carson
Affiliations:
Janssen Research & Development, LLC,Spring House, PA,États-unis;Janssen Research & Development, LLC,Spring House, PA,Vereinigte Staaten;Janssen Research & Development, LLC,Spring House, PA,Stati Uniti;Janssen Research & Development, LLC,Spring House, PA,United States;Janssen Research & Development, LLC,Spring House, PA,Estados Unidos;Janssen Research &am
Laura E. Hogan
Affiliations:
Department of Pediatrics,Stony Brook Children's,Stony Brook, NY,États-unis;Department of Pediatrics,Stony Brook Children's,Stony Brook, NY,Vereinigte Staaten;Department of Pediatrics,Stony Brook Children's,Stony Brook, NY,Stati Uniti;Department of Pediatrics,Stony Brook Children's,Stony Brook, NY,United States;Department of Pediatrics,Stony Brook Children's,Stony Brook, NY,Estados Unidos;Departmen
(Abstract release date: 05/26/22) EHA Library. Vora A. 06/10/22; 357223; P360
Prof. Dr. Ajay Vora
Prof. Dr. Ajay Vora
Contributions
Abstract
Presentation during EHA2022: All (e)Poster presentations will be made available as of Friday, June 10, 2022 (09:00 CEST) and will be accessible for on-demand viewing until Monday, August 15, 2022 on the Congress platform.

Abstract: P360

Type: Poster presentation

Session title: Acute lymphoblastic leukemia - Clinical

Background
Approximately 15-20% of pediatric patients with T-cell acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma (LL) will be refractory to/relapse after frontline treatment; relapsed disease is associated with poor outcomes. In a phase 2 study, 2 of 7 (28.6%) patients with T-cell ALL in first relapse achieved a complete response (CR) using the vincristine, prednisone, PEG-asparaginase, and doxorubicin (VPLD) reinduction backbone. Daratumumab (DARA), a human IgGκ monoclonal antibody targeting CD38 approved for treating multiple myeloma, has shown preclinical efficacy in ALL models.

Aims
Here we report the initial results of DARA plus VPLD in pediatric and young adult patients with relapsed/refractory T-cell ALL or LL enrolled in the phase 2, open-label DELPHINUS study.

Methods
Eligible patients were aged 1-30 y, had T-cell ALL or LL in first relapse or refractory to 1 prior induction/consolidation regimen, and had a performance status ≥70. DARA (16 mg/kg IV QW) was given with VPLD in Cycle 1 and with methotrexate, cyclophosphamide, cytarabine, and 6-mercaptopurine in Cycle 2. Patients received age/risk-adjusted intrathecal therapy. Response was measured at the end of each cycle by local bone marrow morphology. The primary endpoint for ALL patients was CR rate in pediatric patients at the end of Cycle 1. Patients achieving CR after Cycles 1 or 2 could proceed to allogeneic HSCT off study. Overall response rate (ORR) was defined as CR or CR with incomplete hematological recovery (CRi) at any time before start of subsequent therapy or HSCT. Minimal residual disease (MRD) negativity (<0.01%) at any time before disease progression, start of subsequent therapy, or HSCT was centrally reviewed by flow cytometry.

Results
Twenty-four pediatric (age 1-17 y) and 5 young adult (age 18-30 y) ALL patients and 10 LL patients (age 1-30 y) received ≥1 DARA dose. Median (range) age was 10.0 (2-25) y (ALL) and 14.5 (5-22) y (LL); median (range) time from initial diagnosis to first study treatment was 2.0 (0.1-6.1) y (ALL) and 0.8 (0.5-6.0) y (LL). Pediatric ALL patients received a median (range) of 2 (1-3) treatment cycles; young adult ALL patients and LL patients each received 2 (1-2). Among pediatric ALL patients, 10 (41.7%) patients (90% CI, 24.6-60.3) achieved CR at the end of Cycle 1. ORR was 83.3% (CR, 13 [54.2%] patients; CRi, 7 [29.2%] patients) in pediatric and 60.0% (all CR) in young adult ALL patients and 40.0% (all CR) in LL patients. Ten (41.7%) pediatric ALL patients achieved MRD negativity. All pediatric ALL patients had a grade 3/4 TEAE. No pediatric ALL pt discontinued DARA primarily due to AEs and 1 (4.2%) died due to TEAEs (brain edema and hepatic failure) attributed to study treatment but unrelated to DARA.

Conclusion
The addition of DARA to VPLD in pediatric and young adult patients with relapsed/refractory T-cell ALL or LL showed initial activity, generating improved response rates compared to those achieved with backbone therapy alone, with a manageable safety profile.

Keyword(s): CD38, Immune therapy, Multiple myeloma



© 2022 American Society of Clinical Oncology, Inc. Reused with permission. This abstract was accepted and previously presented at the 2022 ASCO Annual Meeting. All rights reserved.
Presentation during EHA2022: All (e)Poster presentations will be made available as of Friday, June 10, 2022 (09:00 CEST) and will be accessible for on-demand viewing until Monday, August 15, 2022 on the Congress platform.

Abstract: P360

Type: Poster presentation

Session title: Acute lymphoblastic leukemia - Clinical

Background
Approximately 15-20% of pediatric patients with T-cell acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma (LL) will be refractory to/relapse after frontline treatment; relapsed disease is associated with poor outcomes. In a phase 2 study, 2 of 7 (28.6%) patients with T-cell ALL in first relapse achieved a complete response (CR) using the vincristine, prednisone, PEG-asparaginase, and doxorubicin (VPLD) reinduction backbone. Daratumumab (DARA), a human IgGκ monoclonal antibody targeting CD38 approved for treating multiple myeloma, has shown preclinical efficacy in ALL models.

Aims
Here we report the initial results of DARA plus VPLD in pediatric and young adult patients with relapsed/refractory T-cell ALL or LL enrolled in the phase 2, open-label DELPHINUS study.

Methods
Eligible patients were aged 1-30 y, had T-cell ALL or LL in first relapse or refractory to 1 prior induction/consolidation regimen, and had a performance status ≥70. DARA (16 mg/kg IV QW) was given with VPLD in Cycle 1 and with methotrexate, cyclophosphamide, cytarabine, and 6-mercaptopurine in Cycle 2. Patients received age/risk-adjusted intrathecal therapy. Response was measured at the end of each cycle by local bone marrow morphology. The primary endpoint for ALL patients was CR rate in pediatric patients at the end of Cycle 1. Patients achieving CR after Cycles 1 or 2 could proceed to allogeneic HSCT off study. Overall response rate (ORR) was defined as CR or CR with incomplete hematological recovery (CRi) at any time before start of subsequent therapy or HSCT. Minimal residual disease (MRD) negativity (<0.01%) at any time before disease progression, start of subsequent therapy, or HSCT was centrally reviewed by flow cytometry.

Results
Twenty-four pediatric (age 1-17 y) and 5 young adult (age 18-30 y) ALL patients and 10 LL patients (age 1-30 y) received ≥1 DARA dose. Median (range) age was 10.0 (2-25) y (ALL) and 14.5 (5-22) y (LL); median (range) time from initial diagnosis to first study treatment was 2.0 (0.1-6.1) y (ALL) and 0.8 (0.5-6.0) y (LL). Pediatric ALL patients received a median (range) of 2 (1-3) treatment cycles; young adult ALL patients and LL patients each received 2 (1-2). Among pediatric ALL patients, 10 (41.7%) patients (90% CI, 24.6-60.3) achieved CR at the end of Cycle 1. ORR was 83.3% (CR, 13 [54.2%] patients; CRi, 7 [29.2%] patients) in pediatric and 60.0% (all CR) in young adult ALL patients and 40.0% (all CR) in LL patients. Ten (41.7%) pediatric ALL patients achieved MRD negativity. All pediatric ALL patients had a grade 3/4 TEAE. No pediatric ALL pt discontinued DARA primarily due to AEs and 1 (4.2%) died due to TEAEs (brain edema and hepatic failure) attributed to study treatment but unrelated to DARA.

Conclusion
The addition of DARA to VPLD in pediatric and young adult patients with relapsed/refractory T-cell ALL or LL showed initial activity, generating improved response rates compared to those achieved with backbone therapy alone, with a manageable safety profile.

Keyword(s): CD38, Immune therapy, Multiple myeloma



© 2022 American Society of Clinical Oncology, Inc. Reused with permission. This abstract was accepted and previously presented at the 2022 ASCO Annual Meeting. All rights reserved.

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