CTLA-4 Blockade Resistance after Relatlimab and Nivolumab

• Published in: The New England journal of medicine Vol. 386; no. 17; pp. 1668 - 1669
• Main Authors: Menzies, Alexander M, Pires da Silva, Ines, Trojaniello, Claudia, Vieu, Elisabeth, Amaria, Rodabe N, Zimmer, Lisa, Lo, Serigne N, Burton, Elizabeth M, Tawbi, Hussein A, Schadendorf, Dirk, Grob, Jean J, Ascierto, Paolo A, Long, Georgina V
• Format: Journal Article
• Language: English
• Published: United States Massachusetts Medical Society 28.04.2022
• Subjects: Antibodies; Antibodies, Monoclonal - adverse effects; Antibodies, Monoclonal - therapeutic use; Antibodies, Monoclonal, Humanized - adverse effects; Antibodies, Monoclonal, Humanized - therapeutic use; Antigens; Antineoplastic Agents, Immunological - adverse effects; Antineoplastic Agents, Immunological - therapeutic use; CD223 antigen; Confidence intervals; Cross-resistance; CTLA-4 Antigen - antagonists & inhibitors; CTLA-4 protein; Cytotoxicity; Dermatology; Drug Resistance; Drug Resistance, Neoplasm; Hematology; Humans; Immune checkpoint inhibitors; Immune Checkpoint Inhibitors - adverse effects; Immune Checkpoint Inhibitors - therapeutic use; Immunotherapy; Lymphocytes; Melanoma; Metastases; Nivolumab - adverse effects; Nivolumab - therapeutic use; Oncology; PD-1 protein; Skin Cancer; Treatments in Oncology; Tumors
• ISSN: 0028-4793; 1533-4406; 1533-4406
• DOI: 10.1056/NEJMc2119768

Data were pooled from 36 patients who received the anti–CTLA-4 antibody ipilimumab after metastatic melanoma progression during therapy with nivolumab (anti–PD-1) plus relatlimab (anti–LAG-3) to assess whether immunotherapies that target distinct checkpoints have different mechanisms of action. The findings suggest that cross-resistance emerges when tumors progress with immune checkpoint inhibitors.