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CTLA-4 Blockade Resistance after Relatlimab and Nivolumab

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.

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Alexander M. Menzies, M.D., Ph.D.
Ines Pires da Silva, M.D., Ph.D.
Melanoma Institute Australia, Sydney, NSW, Australia

Claudia Trojaniello, M.D.
Istituto Nazionale Tumori IRCCS Fondazione Pascale, Naples, Italy

Elisabeth Vieu
Assistance Publique–Hôpitaux de Marseille Timone, Marseille, France

Rodabe N. Amaria, M.D.
University of Texas M.D. Anderson Cancer Center, Houston, TX

Lisa Zimmer, M.D.
University Hospital Essen, Essen, Germany

Serigne N. Lo, Ph.D.
Melanoma Institute Australia, Sydney, NSW, Australia

Elizabeth M. Burton, B.Sc.
Hussein A. Tawbi, M.D., Ph.D.
University of Texas M.D. Anderson Cancer Center, Houston, TX

Dirk Schadendorf, M.D.
University Hospital Essen, Essen, Germany

Jean J. Grob, M.D.
Assistance Publique–Hôpitaux de Marseille Timone, Marseille, France

Paolo A. Ascierto, M.D.
Istituto Nazionale Tumori IRCCS Fondazione Pascale, Naples, Italy

Georgina V. Long, M.D., Ph.D.
Melanoma Institute Australia, Sydney, NSW, Australia

Funding and Disclosures

Disclosure forms provided by the authors are available with the full text of this letter at NEJM.org.

Drs. Menzies and Pires da Silva contributed equally to this letter.

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