Safety and efficacy of odronextamab in patients with relapsed or refractory follicular lymphoma.

Follicular lymphoma bispecific antibody clinical trial odronextamab

Journal

Annals of oncology : official journal of the European Society for Medical Oncology
ISSN: 1569-8041
Titre abrégé: Ann Oncol
Pays: England
ID NLM: 9007735

Informations de publication

Date de publication:
13 Aug 2024
Historique:
received: 05 07 2024
accepted: 06 08 2024
medline: 16 8 2024
pubmed: 16 8 2024
entrez: 15 8 2024
Statut: aheadofprint

Résumé

Odronextamab, a CD20×CD3 bispecific antibody that engages cytotoxic T cells to destroy malignant B cells, has demonstrated encouraging activity across multiple subtypes of relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma. This phase II study (ELM-2; NCT03888105) evaluated odronextamab in patients with R/R follicular lymphoma (FL) after ≥2 lines of systemic therapy. Patients received intravenous odronextamab in 21-day cycles, with step-up dosing in Cycle 1 to help mitigate the risk of cytokine release syndrome (CRS), until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) by independent central review. Among 128 patients evaluated, 95% completed Cycle 1, and 85% completed ≥4 cycles. At 20.1 months' efficacy follow-up, ORR was 80.0% and complete response rate was 73.4%. Median duration of complete response was 25.1 months. Median progression-free survival was 20.7 months, and median overall survival was not reached. Discontinuation of odronextamab due to adverse events (AEs) occurred in 16% of patients. The most common treatment-emergent AEs were CRS (56%; grade ≥3 1.7% [1/60] with 0.7/4/20 mg step-up), neutropenia (39%), and pyrexia (38%). Odronextamab achieved high complete response rates with generally manageable safety in patients with heavily pretreated R/R FL.

Sections du résumé

BACKGROUND BACKGROUND
Odronextamab, a CD20×CD3 bispecific antibody that engages cytotoxic T cells to destroy malignant B cells, has demonstrated encouraging activity across multiple subtypes of relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma.
PATIENTS AND METHODS METHODS
This phase II study (ELM-2; NCT03888105) evaluated odronextamab in patients with R/R follicular lymphoma (FL) after ≥2 lines of systemic therapy. Patients received intravenous odronextamab in 21-day cycles, with step-up dosing in Cycle 1 to help mitigate the risk of cytokine release syndrome (CRS), until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) by independent central review.
RESULTS RESULTS
Among 128 patients evaluated, 95% completed Cycle 1, and 85% completed ≥4 cycles. At 20.1 months' efficacy follow-up, ORR was 80.0% and complete response rate was 73.4%. Median duration of complete response was 25.1 months. Median progression-free survival was 20.7 months, and median overall survival was not reached. Discontinuation of odronextamab due to adverse events (AEs) occurred in 16% of patients. The most common treatment-emergent AEs were CRS (56%; grade ≥3 1.7% [1/60] with 0.7/4/20 mg step-up), neutropenia (39%), and pyrexia (38%).
CONCLUSIONS CONCLUSIONS
Odronextamab achieved high complete response rates with generally manageable safety in patients with heavily pretreated R/R FL.

Identifiants

pubmed: 39147364
pii: S0923-7534(24)03759-1
doi: 10.1016/j.annonc.2024.08.2239
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Auteurs

T M Kim (TM)

Seoul National University Hospital, Seoul, South Korea. Electronic address: gabriel9@snu.ac.kr.

M Taszner (M)

Department of Haematology and Transplantology, Faculty of Medicine, Medical University of Gdańsk, Gdańsk, Poland.

S Novelli (S)

Hematology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.

S-G Cho (SG)

Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, South Korea.

J C Villasboas (JC)

Mayo Clinic, Rochester, USA.

M Merli (M)

Hematology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.

A J Ubieto (AJ)

Hematology Department, Hospital Universitario 12 de Octubre, Madrid, Spain.

B Tessoulin (B)

Hematology Department, Nantes University Hospital, Nantes, France.

L M Poon (LM)

Hematology Oncology National University Hospital, Singapore.

D Tucker (D)

Department of Hematology, Royal Cornwall Hospital, Truro, UK.

J Walewski (J)

Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie Państwowy Instytut Badawczy, Warszawa, Poland.

S Yi (S)

State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China.

Y Song (Y)

Department of Lymphoma, Peking University Cancer Hospital & Institute (Beijing Cancer Hospital), Beijing, China.

G Chong (G)

Department of Medical Oncology, and Clinical Haematology, Olivia Newton-John Cancer Centre, Heidelberg, Australia.

E Bachy (E)

Department of Hematology, Lyon Sud Hospital, Lyon, France; Lymphoma Immuno-Biology (LIB) team, Inserm U1111, CIRI, Lyon, France.

S Guidez (S)

Centre Hospitalier Universitaire (CHU) de Poitiers, Poitiers, France.

A Alonso (A)

Hospital Universitario Quiron Salud Madrid, Madrid, Spain.

D Jagadeesh (D)

Department of Hematology and Medical Oncology, Cleveland Clinic, Cleveland, USA.

W Zhang (W)

Hematology Department, Peking Union Medical College Hospital, Beijing, China.

L Magnano (L)

Hematology Department, Hospital Clínic of Barcelona, Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.

E Iskierka-Jażdżewska (E)

Copernicus Memorial Hospital, Department of General Hematology, Medical University of Łódź, Łódź, Poland.

M Tani (M)

Hematology Unit, Santa Maria delle Croci Hospital, Ravenna, Italy.

B Shen (B)

Regeneron Pharmaceuticals, Inc., Tarrytown, USA.

A Uppala (A)

Regeneron Pharmaceuticals, Inc., Tarrytown, USA.

M Zhu (M)

Regeneron Pharmaceuticals, Inc., Tarrytown, USA.

S Shariff (S)

Regeneron UK Ltd., Uxbridge, UK.

J Brouwer-Visser (J)

Regeneron Pharmaceuticals, Inc., Tarrytown, USA.

A Chaudhry (A)

Regeneron Pharmaceuticals, Inc., Tarrytown, USA.

H Mohamed (H)

Regeneron Pharmaceuticals, Inc., Tarrytown, USA.

S Ambati (S)

Regeneron Pharmaceuticals, Inc., Tarrytown, USA.

S Luminari (S)

Division of Hematology, Azienda Unità Sanitaria Locale-IRCCS, Reggio Emilia, Italy.

Classifications MeSH