The most troublesome thing about cancer is relapse . If the cancer does not recur, it will be much easier to treat. Recently, a clinical trial achieved a 1-year recurrence rate of 0%.
The drug used in this study is a combination of two immunotherapeutic drugs O+R: PD-1 antibody O drug combined with Lag-3 antibody relatlimab. Of the 30 resectable locally advanced melanoma patients who participated in the study, 70% experienced pathological remission to varying degrees. For patients with pathological remission, the 1-year recurrence-free survival rate was 100%, and the 2-year recurrence-free survival rate also reached 92% .
Moreover, compared with the previous PD-1+CTLA-4 dual immunotherapy, the incidence of serious adverse reactions of 73% to 90% and the operation delay rate of 27% [2], only 26% of patients with O+R combination experienced serious immune-related adverse events in the adjuvant treatment stage, and no one postponed the operation due to adverse reactions. O+R can be regarded as the "king" combination in dual immunotherapy.
O+R "King Bang" combination
Immunotherapy has become a major method of cancer treatment, and is used in preoperative neoadjuvant treatment, postoperative adjuvant treatment, and treatment of advanced cancer. For example, in locally advanced melanoma, using PD-1 alone in the adjuvant treatment stage can reduce the patient's risk of recurrence by about half [3].
, and the start time of immunotherapy is advanced to the neoadjuvant treatment stage before the operation, and the single immunotherapy using only PD-1 to dual immunotherapy using PD-1 and CTLA-4 can further enhance the efficacy, and the complete pathological remission rate can reach about half, but the subsequent occurrence of serious adverse reactions of 73% to 90% and the 27% postponement rate of surgery.
Of course, dual immunotherapy does not specifically refer to the combination of PD-1 and CTLA-4. The emerging immune checkpoint Lag-3 can also be added. Lag-3 is an immune checkpoint molecule present on the surface of effector T cells and Treg cells, and has the function of controlling T cell response, activation and proliferation.
and some studies have also found that in patients with PD-1 resistant treatment, Lag-3 expression level is significantly higher. Lag-3 is a major "backdoor" for tumors to escape PD-1 treatment. Lag-3 inhibitors may be better combined with PD-1 inhibitors. So what is the effect of O+R combination of PD-1+Lag-3?
Lag-3 positive is related to poor therapeutic effect of PD-1
A total of 30 resectable locally advanced melanoma patients were included in this study. All patients received 2 doses of O+R neoadjuvant therapy for (doses of 480 mg and 160 mg, respectively) , and performed surgery at week 9, followed by 10 doses of O+R adjuvant therapy.
In the study, except for one person who had distant metastasis and did not undergo surgery, the remaining 29 patients underwent surgery. Among them, 117 patients in html achieved complete pathological remission, 2 were close to complete pathological remission, 2 were partially pathological remission, the pathological remission rate was 57%, and the pathological remission rate was 70%. After 24.4 months of median follow-up, the 1-year and 2-year relapse-free survival rates of all 30 patients were 97% and 82% , respectively. Among them, the 1-year and 2-year relapse-free survival rates of 21 patients who achieved pathological remission reached 100% and 92% , respectively, and the 1-year and 2-year relapse-free survival rates of patients without pathological response also reached 88% and 55% respectively.
recurrence rates in patients with pathological remission and patients without pathological remission
Safety, no immune-related adverse events of grade 3 or above occurred in the neoadjuvant treatment stage. Except for one patient who canceled the surgery due to distant metastasis, and two patients who postponed the surgery due to myocarditis and the COVID-19 pandemic, which were not related to treatment, all the other 27 patients underwent surgery as planned.
. In the adjuvant treatment stage, only 26% of patients experienced severe immune-related adverse events of (grade 3 or above), and 33% of patients chose to stop adjuvant treatment due to adverse reactions.Compared with the PD-1+CTLA-4 dual immunotherapy, the O+R combination has also made great progress.
paper author Rodabe Amaria said: "We are excited to see that the combination of O+R balances safety and effectiveness without causing any delay in surgery. We hope to provide patients with a new treatment option that will help reduce the risk of recurrence of cancer after surgery."
References:
[1]. Amaria R N, Postow M, Burton E M, et al. Neoadjuvant relatlimab and nivolumab in resectable melanoma[J]. Nature, 2022: 1-6.
[2]. Blank C U, Rozeman E A, Fanchi L F, et al. Neoadjuvant versus adjuvant ipilimumab plus nivolumab in macroscopic stage III melanoma[J]. Nature medicine, 2018, 24(11): 1655-1661
[3]. Eggermont A M M, Blank C U, Mandala M, et al. Adjuvant pembrolizumab versus placebo in resisted stage III melanoma[J]. New England Journal of Medicine, 2018, 378(19): 1789-1801.
