relatlimab (BMS-986016)

Relatlimab, a LAG-3 inhibitor, in combination with nivolumab, a PD-1 inhibitor, has recently emerged as a dual ICI strategy targeting T-cell exhaustion. This case illustrates the potential synergistic effect of sequential LAG-3/PD-1 inhibition followed by radiation therapy in eliciting systemic immune activation in AM. It represents the first reported instance of an abscopal effect associated with relatlimab-based immunotherapy, suggesting that strategic sequencing of immunotherapy and radiation may be critical in overcoming immune resistance in this challenging melanoma subtype.

P2, N=76, Not yet recruiting, National Health Research Institutes, Taiwan

HFCs were exposed for 48h to Nivolumab plus Relatlimab, Ipilimumab, or Atezolizumab, either alone or in triplet combinations. Our findings demonstrate that ICI triplets elicit potent immune activation against cardiomyocytes, providing the first preclinical evidence of direct cardiotoxic potential in this setting. These results highlight the need for enhanced clinical surveillance and cardio-oncology monitoring in patients receiving triple ICI combinations, as these regimens expand in clinical practice.

P1/2, N=83, Completed, Bristol-Myers Squibb | Active, not recruiting --> Completed | N=162 --> 83 | Trial primary completion date: Oct 2025 --> Jul 2025

P2, N=92, Recruiting, Duke University | Not yet recruiting --> Recruiting

P2, N=20, Completed, Dan Zandberg | Active, not recruiting --> Completed

P2, N=266, Completed, Bristol-Myers Squibb | Active, not recruiting --> Completed

P2, N=90, Recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial completion date: Jul 2027 --> Nov 2028 | Trial primary completion date: Jul 2027 --> Nov 2028

P2, N=36, Active, not recruiting, Massachusetts General Hospital | Recruiting --> Active, not recruiting

The major risk factor for ICI myocarditis is the use of combination ICI treatment, especially when relatlimab, a novel anti-LAG-3 (lymphocyte-activation gene 3) antibody, is combined with anti-PD-1 (programmed cell death protein 1) therapy...Treatment with anti-CXCR6 antibody prevented premature lethality, attenuated arrhythmias, and reduced the histological severity of myocarditis, demonstrating that CXCR6+ T cells are necessary for disease pathogenesis. Our findings suggest that ICI myocarditis is driven by an expansion of CXCR6+ T cells and identifies CXCR6 as a putative therapeutic target for this highly morbid condition.

He was ultimately started on mycophenolate mofetil in three months later and tapered off steroids completely...The relatlimab/nivolumab combination was selected because of the lower incidence of irAEs reported in Relativity-047 compared to the CheckMate trials with ipilimumab/nivolumab...Management requires prolonged immune suppression, correction of endocrine abnormalities, and coordination with a multidisciplinary team. Physicians should have a low threshold to pause treatment at early laboratory signs of an evolving irAE.

We present the case of an 81-year-old male with a history of recurrent metastatic melanoma previously treated with nivolumab and relatlimab (Opdualag), who developed a persistent pruritic eruption following initiation of dual PD-1/LAG-3 blockade. Despite discontinuation of immunotherapy six months before dermatologic evaluation and use of multiple topical corticosteroids and oral antihistamines, symptoms persisted...At follow-up, the patient reported persistent activity, receiving intramuscular triamcinolone acetonide and adjunctive therapies, including hydroxyzine, hydrocortisone 2.5% cream (for groin), and triamcinolone 0.1% ointment...This case illustrates the diagnostic and therapeutic challenges in managing ICI-induced BP and highlights the early course of dupilumab therapy, which had not yet produced clinical improvement at the time of last follow-up. Continued therapy was planned, and no adverse effects were reported.