EHA Library - The official digital education library of European Hematology Association (EHA)

CARTITUDE-2 COHORT B: UPDATED CLINICAL DATA AND BIOLOGICAL CORRELATIVE ANALYSES OF CILTACABTAGENE AUTOLEUCEL IN PATIENTS WITH MULTIPLE MYELOMA AND EARLY RELAPSE AFTER INITIAL THERAPY
Author(s): ,
Mounzer E. Agha
Affiliations:
UPMC Hillman Cancer Center,Pittsburgh, PA,États-unis;UPMC Hillman Cancer Center,Pittsburgh, PA,Vereinigte Staaten;UPMC Hillman Cancer Center,Pittsburgh, PA,Stati Uniti;UPMC Hillman Cancer Center,Pittsburgh, PA,United States;UPMC Hillman Cancer Center,Pittsburgh, PA,Estados Unidos;UPMC Hillman Cancer Center,Pittsburgh, PA,Verenigde Staten;UPMC Hillman Cancer Center,Pittsburgh, PA,Estados Unidos;UPM
,
Niels W.C.J. van de Donk
Affiliations:
Amsterdam UMC, Vrije Universiteit Amsterdam,Amsterdam,Pays-bas;Amsterdam UMC, Vrije Universiteit Amsterdam,Amsterdam,Niederlande;Amsterdam UMC, Vrije Universiteit Amsterdam,Amsterdam,Paesi Bassi;Amsterdam UMC, Vrije Universiteit Amsterdam,Amsterdam,Netherland;Amsterdam UMC, Vrije Universiteit Amsterdam,Amsterdam,Países Bajos;Amsterdam UMC, Vrije Universiteit Amsterdam,Amsterdam,Nederland;Amsterdam
,
Adam D. Cohen
Affiliations:
Abramson Cancer Center, University of Pennsylvania,Philadelphia, PA,États-unis;Abramson Cancer Center, University of Pennsylvania,Philadelphia, PA,Vereinigte Staaten;Abramson Cancer Center, University of Pennsylvania,Philadelphia, PA,Stati Uniti;Abramson Cancer Center, University of Pennsylvania,Philadelphia, PA,United States;Abramson Cancer Center, University of Pennsylvania,Philadelphia, PA,Esta
,
Yael C. Cohen
Affiliations:
Tel-Aviv Sourasky (Ichilov) Medical Center and Sackler School of Medicine, Tel Aviv University,Tel Aviv,Israël;Tel-Aviv Sourasky (Ichilov) Medical Center and Sackler School of Medicine, Tel Aviv University,Tel Aviv,Israel;Tel-Aviv Sourasky (Ichilov) Medical Center and Sackler School of Medicine, Tel Aviv University,Tel Aviv,Israele;Tel-Aviv Sourasky (Ichilov) Medical Center and Sackler School of M
,
Sébastien Anguille
Affiliations:
Vaccine and Infectious Disease Institute, University of Antwerp, Edegem, Belgium, Center for Cell Therapy and Regenerative Medicine, Antwerp University Hospital,Edegem, Belgium,Belgique;Vaccine and Infectious Disease Institute, University of Antwerp, Edegem, Belgium, Center for Cell Therapy and Regenerative Medicine, Antwerp University Hospital,Edegem, Belgium,Belgien;Vaccine and Infectious Diseas
,
Tessa Kerre
Affiliations:
University Hospital Ghent,Ghent,Belgique;University Hospital Ghent,Ghent,Belgien;University Hospital Ghent,Ghent,Belgio;University Hospital Ghent,Ghent,Belgium;University Hospital Ghent,Ghent,Bélgica;University Hospital Ghent,Ghent,België;University Hospital Ghent,Ghent,Bélgica;University Hospital Ghent,Ghent,Belgium;University Hospital Ghent,Ghent,Belgien
,
Wilfried Roeloffzen
Affiliations:
University Medical Center Groningen,Groningen,Pays-bas;University Medical Center Groningen,Groningen,Niederlande;University Medical Center Groningen,Groningen,Paesi Bassi;University Medical Center Groningen,Groningen,Netherland;University Medical Center Groningen,Groningen,Países Bajos;University Medical Center Groningen,Groningen,Nederland;University Medical Center Groningen,Groningen,Holanda;Uni
,
Jordan M. Schecter
Affiliations:
Janssen R&D, Raritan,NJ,États-unis;Janssen R&D, Raritan,NJ,Vereinigte Staaten;Janssen R&D, Raritan,NJ,Stati Uniti;Janssen R&D, Raritan,NJ,United States;Janssen R&D, Raritan,NJ,Estados Unidos;Janssen R&D, Raritan,NJ,Verenigde Staten;Janssen R&D, Raritan,NJ,Estados Unidos;Janssen R&D, Raritan,NJ,United States;Janssen R&D, Rarita
,
Kevin C. De Braganca
Affiliations:
Janssen R&D, Raritan,NJ,États-unis;Janssen R&D, Raritan,NJ,Vereinigte Staaten;Janssen R&D, Raritan,NJ,Stati Uniti;Janssen R&D, Raritan,NJ,United States;Janssen R&D, Raritan,NJ,Estados Unidos;Janssen R&D, Raritan,NJ,Verenigde Staten;Janssen R&D, Raritan,NJ,Estados Unidos;Janssen R&D, Raritan,NJ,United States;Janssen R&D, Rarita
,
Helen Varsos
Affiliations:
Janssen R&D, Raritan,NJ,États-unis;Janssen R&D, Raritan,NJ,Vereinigte Staaten;Janssen R&D, Raritan,NJ,Stati Uniti;Janssen R&D, Raritan,NJ,United States;Janssen R&D, Raritan,NJ,Estados Unidos;Janssen R&D, Raritan,NJ,Verenigde Staten;Janssen R&D, Raritan,NJ,Estados Unidos;Janssen R&D, Raritan,NJ,United States;Janssen R&D, Rarita
,
Pankaj Mistry
Affiliations:
Janssen R&D,High Wycombe,Royaume-uni;Janssen R&D,High Wycombe,Vereinigtes Königreich;Janssen R&D,High Wycombe,Regno Unito;Janssen R&D,High Wycombe,United Kingdom;Janssen R&D,High Wycombe,Reino Unido;Janssen R&D,High Wycombe,Verenigd Koninkrijk;Janssen R&D,High Wycombe,Reino Unido;Janssen R&D,High Wycombe,Соединённое Королевство;Jansse
,
Tito Roccia
Affiliations:
Janssen R&D,High Wycombe,Royaume-uni;Janssen R&D,High Wycombe,Vereinigtes Königreich;Janssen R&D,High Wycombe,Regno Unito;Janssen R&D,High Wycombe,United Kingdom;Janssen R&D,High Wycombe,Reino Unido;Janssen R&D,High Wycombe,Verenigd Koninkrijk;Janssen R&D,High Wycombe,Reino Unido;Janssen R&D,High Wycombe,Соединённое Королевство;Jansse
,
Enrique Zudaire
Affiliations:
Janssen R&D, Spring House,PA, United States of America,États-unis;Janssen R&D, Spring House,PA, United States of America,Vereinigte Staaten;Janssen R&D, Spring House,PA, United States of America,Stati Uniti;Janssen R&D, Spring House,PA, United States of America,United States;Janssen R&D, Spring House,PA, United States of America,Estados Unidos;Janssen R&
,
Christina Corsale
Affiliations:
Janssen R&D, Raritan,NJ,États-unis;Janssen R&D, Raritan,NJ,Vereinigte Staaten;Janssen R&D, Raritan,NJ,Stati Uniti;Janssen R&D, Raritan,NJ,United States;Janssen R&D, Raritan,NJ,Estados Unidos;Janssen R&D, Raritan,NJ,Verenigde Staten;Janssen R&D, Raritan,NJ,Estados Unidos;Janssen R&D, Raritan,NJ,United States;Janssen R&D, Rarita
,
Muhammad Akram
Affiliations:
Legend Biotech USA, Piscataway,NJ,États-unis;Legend Biotech USA, Piscataway,NJ,Vereinigte Staaten;Legend Biotech USA, Piscataway,NJ,Stati Uniti;Legend Biotech USA, Piscataway,NJ,United States;Legend Biotech USA, Piscataway,NJ,Estados Unidos;Legend Biotech USA, Piscataway,NJ,Verenigde Staten;Legend Biotech USA, Piscataway,NJ,Estados Unidos;Legend Biotech USA, Piscataway,NJ,United States;Legend Biot
,
Dong Geng
Affiliations:
Legend Biotech USA, Piscataway,NJ,États-unis;Legend Biotech USA, Piscataway,NJ,Vereinigte Staaten;Legend Biotech USA, Piscataway,NJ,Stati Uniti;Legend Biotech USA, Piscataway,NJ,United States;Legend Biotech USA, Piscataway,NJ,Estados Unidos;Legend Biotech USA, Piscataway,NJ,Verenigde Staten;Legend Biotech USA, Piscataway,NJ,Estados Unidos;Legend Biotech USA, Piscataway,NJ,United States;Legend Biot
,
Tonia Nesheiwat
Affiliations:
Legend Biotech USA, Piscataway,NJ,États-unis;Legend Biotech USA, Piscataway,NJ,Vereinigte Staaten;Legend Biotech USA, Piscataway,NJ,Stati Uniti;Legend Biotech USA, Piscataway,NJ,United States;Legend Biotech USA, Piscataway,NJ,Estados Unidos;Legend Biotech USA, Piscataway,NJ,Verenigde Staten;Legend Biotech USA, Piscataway,NJ,Estados Unidos;Legend Biotech USA, Piscataway,NJ,United States;Legend Biot
,
Lida Pacaud
Affiliations:
Legend Biotech USA, Piscataway,NJ,États-unis;Legend Biotech USA, Piscataway,NJ,Vereinigte Staaten;Legend Biotech USA, Piscataway,NJ,Stati Uniti;Legend Biotech USA, Piscataway,NJ,United States;Legend Biotech USA, Piscataway,NJ,Estados Unidos;Legend Biotech USA, Piscataway,NJ,Verenigde Staten;Legend Biotech USA, Piscataway,NJ,Estados Unidos;Legend Biotech USA, Piscataway,NJ,United States;Legend Biot
,
Pieter Sonneveld
Affiliations:
Erasmus MC University and Medical Center,Rotterdam,Pays-bas;Erasmus MC University and Medical Center,Rotterdam,Niederlande;Erasmus MC University and Medical Center,Rotterdam,Paesi Bassi;Erasmus MC University and Medical Center,Rotterdam,Netherland;Erasmus MC University and Medical Center,Rotterdam,Países Bajos;Erasmus MC University and Medical Center,Rotterdam,Nederland;Erasmus MC University and M
Sonja Zweegman
Affiliations:
Amsterdam UMC, Vrije Universiteit Amsterdam,Amsterdam,Pays-bas;Amsterdam UMC, Vrije Universiteit Amsterdam,Amsterdam,Niederlande;Amsterdam UMC, Vrije Universiteit Amsterdam,Amsterdam,Paesi Bassi;Amsterdam UMC, Vrije Universiteit Amsterdam,Amsterdam,Netherland;Amsterdam UMC, Vrije Universiteit Amsterdam,Amsterdam,Países Bajos;Amsterdam UMC, Vrije Universiteit Amsterdam,Amsterdam,Nederland;Amsterdam
(Abstract release date: 05/26/22) EHA Library. E. Agha M. 06/12/22; 357049; S185
Mounzer E. Agha
Mounzer E. Agha
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: S185

Type: Oral Presentation

Session title: Relapsed/refractory myeloma: BCMA-directed therapies

Background
CARTITUDE-2 (NCT04133636) is a phase 2, multicohort study evaluating the efficacy and safety of the chimeric antigen receptor (CAR) T-cell therapy ciltacabtagene autoleucel (cilta-cel) in patients (pts) with multiple myeloma (MM). Cohort B enrolled pts who had early relapse after initial therapy. These pts have functionally high-risk disease, as early relapse following autologous stem cell transplantation (ASCT) is associated with poor prognosis, representing an unmet medical need.

Aims
To present updated results from CARTITUDE-2 cohort B.

Methods
All pts provided informed consent. Pts had MM, received 1 prior line of therapy (proteasome inhibitor and immunomodulatory drug required), had disease progression per International Myeloma Working Group criteria (either ≤12 months after ASCT or ≤12 months after initiation of anti-myeloma therapy for pts not treated with ASCT), and were naive to CAR-T or other anti-B-cell maturation antigen therapies. After lymphodepletion, a single cilta-cel infusion was administered at a target dose of 0.75×106 CAR+ viable T cells/kg. Efficacy and safety were evaluated. The primary endpoint was minimal residual disease (MRD) negativity at 10-5. Patient management strategies were used to minimize risk of movement and neurocognitive adverse events (MNTs). Pharmacokinetic (PK) analyses, including Cmax and Tmax of CAR+ Tcell transgene levels in blood are being performed. Additional assessments include levels of cytokine release syndrome (CRS)related cytokines (eg, IL-6) over time, peak levels of cytokines by response and CRS, association of cytokine levels with immune effector cell-associated neurotoxicity syndrome (ICANS), and CAR+ T cell CD4/CD8 ratio by response, CRS, and ICANS.

Results
19 pts (median age: 58.0 years [range: 44-67]; 74% male) received cilta-cel as of January 2022; 79% received prior ASCT. Median follow-up was 13.4 months (range: 5.2-21.7). Overall response rate was 100.0%, with 90% of pts achieving ≥complete response, and 95% achieving ≥very good partial response. Median time to first response was 0.95 months (range: 0.9-9.7) and median time to best response was 5.1 months (range: 0.9-11.8). Among 15 MRD-evaluable pts, 14 (93%) achieved MRD 10-5 negativity. Median duration of response was not reached. The 12-month progression-free survival rate was 90%; 12-month event-free rate was 88.9%. CRS occurred in 16 (84.2%) pts (1 grade 4); median time to onset was 8 days (range: 5-11) and all events resolved. ICANS (grade 1) and MNT (grade 3, previously reported) occurred in 1 pt each. 1 pt died post cilta-cel (progressive disease, day 158). Preliminary PK data showed peak expansion of CAR-T cells on day 13.1 (range: 8.96-209.9); median persistence was 76.9 days (range: 40.99-221.8).

Conclusion
This functionally high-risk pt population with early relapse after initial therapy experienced deep and durable responses with manageable safety following a single cilta-cel infusion. Cilta-cel led to responses in pts with ineffective or insufficient response to ASCT. Follow-up is ongoing and responses continue to deepen. We will present updated and detailed PK, cytokine, and CAR-T subset analyses as well as clinical correlation to provide insight into biological correlates of efficacy and safety in these pts.

Keyword(s): 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 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: S185

Type: Oral Presentation

Session title: Relapsed/refractory myeloma: BCMA-directed therapies

Background
CARTITUDE-2 (NCT04133636) is a phase 2, multicohort study evaluating the efficacy and safety of the chimeric antigen receptor (CAR) T-cell therapy ciltacabtagene autoleucel (cilta-cel) in patients (pts) with multiple myeloma (MM). Cohort B enrolled pts who had early relapse after initial therapy. These pts have functionally high-risk disease, as early relapse following autologous stem cell transplantation (ASCT) is associated with poor prognosis, representing an unmet medical need.

Aims
To present updated results from CARTITUDE-2 cohort B.

Methods
All pts provided informed consent. Pts had MM, received 1 prior line of therapy (proteasome inhibitor and immunomodulatory drug required), had disease progression per International Myeloma Working Group criteria (either ≤12 months after ASCT or ≤12 months after initiation of anti-myeloma therapy for pts not treated with ASCT), and were naive to CAR-T or other anti-B-cell maturation antigen therapies. After lymphodepletion, a single cilta-cel infusion was administered at a target dose of 0.75×106 CAR+ viable T cells/kg. Efficacy and safety were evaluated. The primary endpoint was minimal residual disease (MRD) negativity at 10-5. Patient management strategies were used to minimize risk of movement and neurocognitive adverse events (MNTs). Pharmacokinetic (PK) analyses, including Cmax and Tmax of CAR+ Tcell transgene levels in blood are being performed. Additional assessments include levels of cytokine release syndrome (CRS)related cytokines (eg, IL-6) over time, peak levels of cytokines by response and CRS, association of cytokine levels with immune effector cell-associated neurotoxicity syndrome (ICANS), and CAR+ T cell CD4/CD8 ratio by response, CRS, and ICANS.

Results
19 pts (median age: 58.0 years [range: 44-67]; 74% male) received cilta-cel as of January 2022; 79% received prior ASCT. Median follow-up was 13.4 months (range: 5.2-21.7). Overall response rate was 100.0%, with 90% of pts achieving ≥complete response, and 95% achieving ≥very good partial response. Median time to first response was 0.95 months (range: 0.9-9.7) and median time to best response was 5.1 months (range: 0.9-11.8). Among 15 MRD-evaluable pts, 14 (93%) achieved MRD 10-5 negativity. Median duration of response was not reached. The 12-month progression-free survival rate was 90%; 12-month event-free rate was 88.9%. CRS occurred in 16 (84.2%) pts (1 grade 4); median time to onset was 8 days (range: 5-11) and all events resolved. ICANS (grade 1) and MNT (grade 3, previously reported) occurred in 1 pt each. 1 pt died post cilta-cel (progressive disease, day 158). Preliminary PK data showed peak expansion of CAR-T cells on day 13.1 (range: 8.96-209.9); median persistence was 76.9 days (range: 40.99-221.8).

Conclusion
This functionally high-risk pt population with early relapse after initial therapy experienced deep and durable responses with manageable safety following a single cilta-cel infusion. Cilta-cel led to responses in pts with ineffective or insufficient response to ASCT. Follow-up is ongoing and responses continue to deepen. We will present updated and detailed PK, cytokine, and CAR-T subset analyses as well as clinical correlation to provide insight into biological correlates of efficacy and safety in these pts.

Keyword(s): 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.

By clicking “Accept Terms & all Cookies” or by continuing to browse, you agree to the storing of third-party cookies on your device to enhance your user experience and agree to the user terms and conditions of this learning management system (LMS).

Cookie Settings
Accept Terms & all Cookies