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EVALUATING TECLISTAMAB IN PATIENTS WITH RELAPSED/ REFRACTORY MULTIPLE MYELOMA FOLLOWING EXPOSURE TO OTHER B-CELL MATURATION ANTIGEN (BCMA)-TARGETED AGENTS
Author(s): ,
Cyrille Touzeau
Affiliations:
University Hospital Hôtel-Dieu,Nantes,France;University Hospital Hôtel-Dieu,Nantes,Frankreich;University Hospital Hôtel-Dieu,Nantes,Francia;University Hospital Hôtel-Dieu,Nantes,France;University Hospital Hôtel-Dieu,Nantes,Francia;University Hospital Hôtel-Dieu,Nantes,Frankrijk;University Hospital Hôtel-Dieu,Nantes,França;University Hospital Hôtel-Dieu,Nantes,Франция ;University Hospital Hôtel-Die
,
Amrita Krishnan
Affiliations:
City of Hope Comprehensive Cancer Center,Duarte,États-unis;City of Hope Comprehensive Cancer Center,Duarte,Vereinigte Staaten;City of Hope Comprehensive Cancer Center,Duarte,Stati Uniti;City of Hope Comprehensive Cancer Center,Duarte,United States;City of Hope Comprehensive Cancer Center,Duarte,Estados Unidos;City of Hope Comprehensive Cancer Center,Duarte,Verenigde Staten;City of Hope Comprehensi
,
Philippe Moreau
Affiliations:
University Hospital Hôtel-Dieu,Nantes,France;University Hospital Hôtel-Dieu,Nantes,Frankreich;University Hospital Hôtel-Dieu,Nantes,Francia;University Hospital Hôtel-Dieu,Nantes,France;University Hospital Hôtel-Dieu,Nantes,Francia;University Hospital Hôtel-Dieu,Nantes,Frankrijk;University Hospital Hôtel-Dieu,Nantes,França;University Hospital Hôtel-Dieu,Nantes,Франция ;University Hospital Hôtel-Die
,
Aurore Perrot
Affiliations:
Centre Hospitalier, Universitaire de Toulouse, Service d'Hematologie,Toulouse,France;Centre Hospitalier, Universitaire de Toulouse, Service d'Hematologie,Toulouse,Frankreich;Centre Hospitalier, Universitaire de Toulouse, Service d'Hematologie,Toulouse,Francia;Centre Hospitalier, Universitaire de Toulouse, Service d'Hematologie,Toulouse,France;Centre Hospitalier, Universitaire de Toulouse, Service
,
Saad Z. Usmani
Affiliations:
Levine Cancer Institute/Atrium Health,Charlotte,États-unis;Levine Cancer Institute/Atrium Health,Charlotte,Vereinigte Staaten;Levine Cancer Institute/Atrium Health,Charlotte,Stati Uniti;Levine Cancer Institute/Atrium Health,Charlotte,United States;Levine Cancer Institute/Atrium Health,Charlotte,Estados Unidos;Levine Cancer Institute/Atrium Health,Charlotte,Verenigde Staten;Levine Cancer Institute/
,
Salomon Manier
Affiliations:
University of Lille,Lille,France;University of Lille,Lille,Frankreich;University of Lille,Lille,Francia;University of Lille,Lille,France;University of Lille,Lille,Francia;University of Lille,Lille,Frankrijk;University of Lille,Lille,França;University of Lille,Lille,Франция ;University of Lille,Lille,Frankrike
,
Michele Cavo
Affiliations:
IRCSS Aziena Ospedaliero-Universitaria di Bologna, Bologna University School of Medicine,Bologna,Italie;IRCSS Aziena Ospedaliero-Universitaria di Bologna, Bologna University School of Medicine,Bologna,Italien;IRCSS Aziena Ospedaliero-Universitaria di Bologna, Bologna University School of Medicine,Bologna,Italia;IRCSS Aziena Ospedaliero-Universitaria di Bologna, Bologna University School of Medicin
,
Carmen Martinez-Chamorro
Affiliations:
University Hospital Quirónsalud, Pozuelo de Alarcón,Madrid,Espagne;University Hospital Quirónsalud, Pozuelo de Alarcón,Madrid,Spanien;University Hospital Quirónsalud, Pozuelo de Alarcón,Madrid,Spagna;University Hospital Quirónsalud, Pozuelo de Alarcón,Madrid,Spain;University Hospital Quirónsalud, Pozuelo de Alarcón,Madrid,España;University Hospital Quirónsalud, Pozuelo de Alarcón,Madrid,Spanje;Uni
,
Ajay Nooka
Affiliations:
Winship Cancer Institute, Emory University,Atlanta,États-unis;Winship Cancer Institute, Emory University,Atlanta,Vereinigte Staaten;Winship Cancer Institute, Emory University,Atlanta,Stati Uniti;Winship Cancer Institute, Emory University,Atlanta,United States;Winship Cancer Institute, Emory University,Atlanta,Estados Unidos;Winship Cancer Institute, Emory University,Atlanta,Verenigde Staten;Winshi
,
Thomas Martin
Affiliations:
University of California, San Francisco,San Francisco,États-unis;University of California, San Francisco,San Francisco,Vereinigte Staaten;University of California, San Francisco,San Francisco,Stati Uniti;University of California, San Francisco,San Francisco,United States;University of California, San Francisco,San Francisco,Estados Unidos;University of California, San Francisco,San Francisco,Veren
,
Lionel Karlin
Affiliations:
Service d'Hématologie Clinique, Centre Hospitalier Lyon Sud,Pierre-Bénite,France;Service d'Hématologie Clinique, Centre Hospitalier Lyon Sud,Pierre-Bénite,Frankreich;Service d'Hématologie Clinique, Centre Hospitalier Lyon Sud,Pierre-Bénite,Francia;Service d'Hématologie Clinique, Centre Hospitalier Lyon Sud,Pierre-Bénite,France;Service d'Hématologie Clinique, Centre Hospitalier Lyon Sud,Pierre-Béni
,
Xavier Leleu
Affiliations:
Centre Hospitalier Universitaire de Poitiers,Poitiers,France;Centre Hospitalier Universitaire de Poitiers,Poitiers,Frankreich;Centre Hospitalier Universitaire de Poitiers,Poitiers,Francia;Centre Hospitalier Universitaire de Poitiers,Poitiers,France;Centre Hospitalier Universitaire de Poitiers,Poitiers,Francia;Centre Hospitalier Universitaire de Poitiers,Poitiers,Frankrijk;Centre Hospitalier Univer
,
Nizar Bahlis
Affiliations:
Arnie Charbonneau Cancer Institute, University of Calgary,Calgary,Canada;Arnie Charbonneau Cancer Institute, University of Calgary,Calgary,Kanada;Arnie Charbonneau Cancer Institute, University of Calgary,Calgary,Canada;Arnie Charbonneau Cancer Institute, University of Calgary,Calgary,Canada;Arnie Charbonneau Cancer Institute, University of Calgary,Calgary,Canadá;Arnie Charbonneau Cancer Institute,
,
Britta Besemer
Affiliations:
University of Tuebingen,Tuebingen,Allemagne;University of Tuebingen,Tuebingen,Deutschland;University of Tuebingen,Tuebingen,Germania;University of Tuebingen,Tuebingen,Germany;University of Tuebingen,Tuebingen,Alemania;University of Tuebingen,Tuebingen,Duitsland;University of Tuebingen,Tuebingen,Alemanha;University of Tuebingen,Tuebingen,Германия;University of Tuebingen,Tuebingen,Tyskland
,
Lixia Pei
Affiliations:
Janssen Research & Development,Raritan,États-unis;Janssen Research & Development,Raritan,Vereinigte Staaten;Janssen Research & Development,Raritan,Stati Uniti;Janssen Research & Development,Raritan,United States;Janssen Research & Development,Raritan,Estados Unidos;Janssen Research & Development,Raritan,Verenigde Staten;Janssen Research & Dev
,
Raluca Verona
Affiliations:
Janssen Research & Development,Spring House,États-unis;Janssen Research & Development,Spring House,Vereinigte Staaten;Janssen Research & Development,Spring House,Stati Uniti;Janssen Research & Development,Spring House,United States;Janssen Research & Development,Spring House,Estados Unidos;Janssen Research & Development,Spring House,Verenigde Staten;
,
Suzette Girgis
Affiliations:
Janssen Research & Development,Spring House,États-unis;Janssen Research & Development,Spring House,Vereinigte Staaten;Janssen Research & Development,Spring House,Stati Uniti;Janssen Research & Development,Spring House,United States;Janssen Research & Development,Spring House,Estados Unidos;Janssen Research & Development,Spring House,Verenigde Staten;
,
Clarissa Uhlar
Affiliations:
Janssen Research & Development,Spring House,États-unis;Janssen Research & Development,Spring House,Vereinigte Staaten;Janssen Research & Development,Spring House,Stati Uniti;Janssen Research & Development,Spring House,United States;Janssen Research & Development,Spring House,Estados Unidos;Janssen Research & Development,Spring House,Verenigde Staten;
,
Rachel Kobos
Affiliations:
Janssen Research & Development,Raritan,États-unis;Janssen Research & Development,Raritan,Vereinigte Staaten;Janssen Research & Development,Raritan,Stati Uniti;Janssen Research & Development,Raritan,United States;Janssen Research & Development,Raritan,Estados Unidos;Janssen Research & Development,Raritan,Verenigde Staten;Janssen Research & Dev
Alfred Garfall
Affiliations:
Abramson Cancer Center, Perelman School of Medicine,Philadelphia,États-unis;Abramson Cancer Center, Perelman School of Medicine,Philadelphia,Vereinigte Staaten;Abramson Cancer Center, Perelman School of Medicine,Philadelphia,Stati Uniti;Abramson Cancer Center, Perelman School of Medicine,Philadelphia,United States;Abramson Cancer Center, Perelman School of Medicine,Philadelphia,Estados Unidos;Abra
(Abstract release date: 05/26/22) EHA Library. Touzeau C. 06/11/22; 357048; S184
Cyrille Touzeau
Cyrille Touzeau
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: S184

Type: Oral Presentation

Session title: Relapsed/refractory myeloma: Bispecific antibodies

Background
Teclistamab (JNJ-64007957) is a T cell redirecting bispecific antibody that targets both B-cell maturation antigen (BCMA) and CD3 receptors to induce T cell mediated cytotoxicity of BCMA-expressing myeloma cells. MajesTEC-1 is an open-label, multicohort, phase 1/2 study evaluating teclistamab in patients (pts) with relapsed/ refractory multiple myeloma (RRMM) previously treated with ≥3 prior lines of therapy (LOT). An overall response rate (ORR) of 62.0% in pts with no prior anti-BCMA treatment (tx) was previously reported in a pooled analysis from phase 1 and phase 2 cohort A at a median follow-up of 7.8 mo.

Aims
We report efficacy and safety results of teclistamab from cohort C, which enrolled patients who had prior exposure to anti-BCMA treatment.

Methods
Eligible pts (age ≥18 y) had multiple myeloma (MM) per IMWG criteria and were previously treated with ≥3 prior LOT, including a PI, IMiD, anti-CD38 antibody, and anti-BCMA treatment (chimeric antigen receptor T cell therapy [CAR-T] or Ab drug conjugate [ADC]). Pts were enrolled using a Simon’s stage design to receive weekly subcutaneous teclistamab 1.5 mg/kg (step-up doses of 0.06 and 0.3 mg/kg). ORR per IMWG 2016 criteria was the primary endpoint. All AEs were graded per CTCAE v4.03; immune effector cell–associated neurotoxicity syndrome (ICANS) and cytokine release syndrome (CRS) were graded per ASTCT guidelines.

Results
In cohort C, 38 pts (median age 63.5 y [range 32–82]; 63% male) received teclistamab (median prior LOT 6 [range 3–14]) at the data cutoff date of Sep 7, 2021. Of the 38 patients, 25 (66%) were refractory to an anti-BCMA treatment, and 32 (84%) were refractory to last LOT. Among 25 efficacy-evaluable patients, 16 (64%) received prior ADC, 11 (44%) received prior CAR-T, and 2 pts received both. The ORR was 40% (95% CI, 21–61) at a median follow-up of 6.9 mo (range 0.7–8.7). Complete response or better were observed in 5 pts (20%). In ADC-exposed and CAR-T-exposed pts, the ORR was 38% (95% CI, 15–65) and 45% (95% CI, 17–77), respectively. Responses were rapid in most, with deepening of responses over time in 7 of 25 pts. While the median duration of response was not reached, median time to first response was 1.2 mo (range, 0.2–4.9) and to best response was 2.1 mo (range, 1.1–5.7). No new safety concerns were observed, and the safety profile was comparable with that of BMCA tx-naive pts. Infections were reported in 16 pts (42%; grade 3/4, 26%). Most common AEs (n=38) were CRS (63%; all grade 1/2; median time to CRS onset: 3 d [range, 2–6], duration of CRS: 2 d [range, 1–4]), thrombocytopenia (42%; grade 3/4, 29%), neutropenia (55%; grade 3/4, 50%), lymphopenia (40%; grade 3/4, 37%), and  anemia (39%; grade 3/4 29%), Grade 3 ICANS was reported in 1 pt which resolved with supportive care and the pt remained on tx. Anti-teclistamab Abs were not detected in any pts. Baseline BCMA expression levels were comparable with those reported in BCMA tx-naive pts. Updated efficacy and safety results will be presented for 40 pts.

Conclusion
These preliminary results observed with serial targeting of BCMA with teclistamab following ADC or CAR‑T tx suggest a promising ORR with early responses that deepen over time. Additionally, a well-tolerated safety profile was observed in patients treated with anti-BCMA tx.

Keyword(s): B-cell maturation antigen, Bispecific, 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: S184

Type: Oral Presentation

Session title: Relapsed/refractory myeloma: Bispecific antibodies

Background
Teclistamab (JNJ-64007957) is a T cell redirecting bispecific antibody that targets both B-cell maturation antigen (BCMA) and CD3 receptors to induce T cell mediated cytotoxicity of BCMA-expressing myeloma cells. MajesTEC-1 is an open-label, multicohort, phase 1/2 study evaluating teclistamab in patients (pts) with relapsed/ refractory multiple myeloma (RRMM) previously treated with ≥3 prior lines of therapy (LOT). An overall response rate (ORR) of 62.0% in pts with no prior anti-BCMA treatment (tx) was previously reported in a pooled analysis from phase 1 and phase 2 cohort A at a median follow-up of 7.8 mo.

Aims
We report efficacy and safety results of teclistamab from cohort C, which enrolled patients who had prior exposure to anti-BCMA treatment.

Methods
Eligible pts (age ≥18 y) had multiple myeloma (MM) per IMWG criteria and were previously treated with ≥3 prior LOT, including a PI, IMiD, anti-CD38 antibody, and anti-BCMA treatment (chimeric antigen receptor T cell therapy [CAR-T] or Ab drug conjugate [ADC]). Pts were enrolled using a Simon’s stage design to receive weekly subcutaneous teclistamab 1.5 mg/kg (step-up doses of 0.06 and 0.3 mg/kg). ORR per IMWG 2016 criteria was the primary endpoint. All AEs were graded per CTCAE v4.03; immune effector cell–associated neurotoxicity syndrome (ICANS) and cytokine release syndrome (CRS) were graded per ASTCT guidelines.

Results
In cohort C, 38 pts (median age 63.5 y [range 32–82]; 63% male) received teclistamab (median prior LOT 6 [range 3–14]) at the data cutoff date of Sep 7, 2021. Of the 38 patients, 25 (66%) were refractory to an anti-BCMA treatment, and 32 (84%) were refractory to last LOT. Among 25 efficacy-evaluable patients, 16 (64%) received prior ADC, 11 (44%) received prior CAR-T, and 2 pts received both. The ORR was 40% (95% CI, 21–61) at a median follow-up of 6.9 mo (range 0.7–8.7). Complete response or better were observed in 5 pts (20%). In ADC-exposed and CAR-T-exposed pts, the ORR was 38% (95% CI, 15–65) and 45% (95% CI, 17–77), respectively. Responses were rapid in most, with deepening of responses over time in 7 of 25 pts. While the median duration of response was not reached, median time to first response was 1.2 mo (range, 0.2–4.9) and to best response was 2.1 mo (range, 1.1–5.7). No new safety concerns were observed, and the safety profile was comparable with that of BMCA tx-naive pts. Infections were reported in 16 pts (42%; grade 3/4, 26%). Most common AEs (n=38) were CRS (63%; all grade 1/2; median time to CRS onset: 3 d [range, 2–6], duration of CRS: 2 d [range, 1–4]), thrombocytopenia (42%; grade 3/4, 29%), neutropenia (55%; grade 3/4, 50%), lymphopenia (40%; grade 3/4, 37%), and  anemia (39%; grade 3/4 29%), Grade 3 ICANS was reported in 1 pt which resolved with supportive care and the pt remained on tx. Anti-teclistamab Abs were not detected in any pts. Baseline BCMA expression levels were comparable with those reported in BCMA tx-naive pts. Updated efficacy and safety results will be presented for 40 pts.

Conclusion
These preliminary results observed with serial targeting of BCMA with teclistamab following ADC or CAR‑T tx suggest a promising ORR with early responses that deepen over time. Additionally, a well-tolerated safety profile was observed in patients treated with anti-BCMA tx.

Keyword(s): B-cell maturation antigen, Bispecific, 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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