Sure melanoma sufferers (these with locoregionally superior, resectable melanoma) have a excessive danger of relapse and demise from the most cancers. Some, these with clinically detected nodal illness, have a mortality danger as excessive as 75%.
Earlier work—by the Checkmate-915 trial—investigated if the addition of ipilimumab to nivolumab within the adjuvant setting improved recurrence-free survival (RFS) in comparison with nivolumab alone. Not solely did it not work, it elevated toxicity.
Now, a gaggle has discovered that giving the mix of immune checkpoint inhibitors relatlimab and nivolumab within the neoadjuvant (pre-surgery) setting to sufferers with stage III melanoma was secure and fully cleared all viable tumor in 57% of sufferers in a Section II examine.
Along with assembly the first endpoint of pathologic full response (pCR), the general pathologic response fee (as much as 50% of viable tumor left on the time of surgical procedure) was 70%. No sufferers had grade 3 or 4 immune-related hostile occasions (IRAE) within the neoadjuvant setting or confirmed toxicity-related surgical delays.
This analysis seems in Nature within the article, “Neoadjuvant relatlimab and nivolumab in resectable melanoma.”
“With scientific stage III melanoma, the chance that the most cancers comes again after surgical procedure might be as excessive as 50%. One of many targets of neoadjuvant immunotherapy is to scale back the prospect of recurrence by evaluating remedies in earlier stage, operable illness which have been profitable for stage IV melanoma,” mentioned lead/corresponding writer Rodabe Amaria, MD, affiliate professor of melanoma medical oncology on the College of Texas MD Anderson Most cancers Middle. “Our findings help the mix of relatlimab and nivolumab as a secure and efficient remedy possibility within the neoadjuvant setting for stage III melanoma.”
Relatlimab is a novel immune checkpoint inhibitor that blocks LAG-3, which is discovered on the floor of T cells and sometimes is upregulated in melanoma. Nivolumab is a PD-1 inhibitor. The FDA authorised the identical mixture for stage IV melanoma in March 2022 primarily based on outcomes of the RELATIVITY-047 examine printed within the New England Journal of Medication in January 2022.
The present examine enrolled 30 sufferers at MD Anderson and Memorial Sloan Kettering Most cancers Middle to obtain two doses of neoadjuvant relatlimab and nivolumab, adopted by surgical procedure and 10 doses of the identical mixture within the adjuvant setting. One affected person developed a mind metastasis throughout neoadjuvant remedy and didn’t proceed to surgical procedure. The median age of sufferers was 60, and 63% of sufferers had been male.
After a median of 24.4 months follow-up within the 29 sufferers who underwent surgical procedure, the speed of recurrence-free survival was 97% at one 12 months and 82% at two years. RFS charges had been highest in sufferers with a pCR: 100% at one 12 months and 91% at two years, in comparison with 92% and 69% in sufferers and not using a pCR. The one- and two-year total survival charges for all sufferers had been 93% and 88%, respectively.
No grade 3 or 4 IRAEs occurred through the eight weeks of neoadjuvant remedy. One affected person’s surgical procedure was delayed on account of asymptomatic myocarditis, which was decided to be unrelated to remedy. Throughout adjuvant remedy, 26% of sufferers developed grade 3 or 4 IRAEs, with secondary adrenal insufficiency and elevated liver enzymes being two of the commonest unwanted effects.
The outcomes are favorable in relation to 2 prior examine arms, which assessed nivolumab both alone or together with the CTLA-4 checkpoint inhibitor ipilimumab. These outcomes, reported by Amaria and colleagues in Nature Medication in 2018, confirmed a pCR fee of 45%, with 73% of sufferers experiencing grade 3 unwanted effects within the mixture arm. The nivolumab monotherapy arm achieved a pCR fee of 25%, with 8% of sufferers experiencing grade 3 unwanted effects. The excessive toxicity fee led to early closure of the earlier examine.
“We’re more than happy to see that the mix of relatlimab and nivolumab balanced security and efficacy, and it didn’t end in any delays to surgical procedure,” Amaria mentioned. “We need to present sufferers with a remedy possibility that may assist cut back the chance of their most cancers returning after surgical procedure. Our information complement the RELATIVITY-047 examine outcomes and supply additional proof to help the usage of this mix in melanoma.”