In a study reported as a letter to the editor in The New England Journal of Medicine, Alexander M. Menzies, MD, and colleagues found that patients with metastatic melanoma who had progressive disease while receiving relatlimab/nivolumab had poor responses to anti–CTLA-4–based treatment.
Alexander M. Menzies, MD
As noted by the investigators, the recently reported RELATIVITY-047 trial showed improved progression-free survival with the combination of the anti–LAG-3 antibody relatlimab plus nivolumab vs nivolumab alone in previously untreated patients with metastatic melanoma. They further noted that in disease refractory to PD-1 inhibition, use of an anti–CTLA-4 antibody alone or combined with an anti–PD-1 antibody has shown meaningful activity, with this finding suggesting nonoverlapping mechanisms of antitumor immune activity.
Study Details
The study involved pooled retrospective data on 36 patients from five international centers who experienced disease progression while receiving relatlimab/nivolumab who were subsequently treated with an anti–CTLA-4 antibody alone (n = 19) or in combination with an anti–PD-1 antibody (n = 17).
Best initial response to relatlimab/nivolumab was complete/partial response in 5 patients, stable or progressive disease in 27, and not available in 4.
Key Findings
Median follow-up was 16.8 months (95% confidence interval [CI] = 11.5 months–not reached).
Objective response with anti–CTLA-4-based treatment was achieved in four patients (11%).
Median progression-free survival was 2.6 months (95% CI = 2.1–3.2 months), with a 1-year rate of 8%. Median overall survival was 9.6 months (95% CI = 6.2 months–not reached), with a 1-year rate of 46%.
The number of patients included in the study was too small to allow for a meaningful comparison of activity with anti–CTLA-4 antibody vs anti–CTLA-4 combined with anti–PD-1 antibody treatment.
As stated by the investigators, “These early data suggest that tumors that are refractory to immunotherapy directed at PD-1 and LAG-3 are unlikely to respond to CTLA-4–targeted therapy.”
Dr. Menzies, and Ines Pires da Silva, MD, PhD, both of the Melanoma Institute Australia, Sydney, contributed equally to The New England Journal of Medicine article.
Disclosure: For full disclosures of the study authors, visit nejm.org.
