Immune Checkpoint Inhibitors for Solid Tumors in the Adjuvant Setting: Current Progress, Future Directions, and Role in Transplant Oncology

Abstract

The rationale for administering immune checkpoint inhibitors (ICIs) in the adjuvant setting is to eradicate micro-metastases and, ultimately, prolong survival. Thus far, clinical trials have demonstrated that 1-year adjuvant courses of ICIs reduce the risk of recurrence in melanoma, urothelial cancer, renal cell carcinoma, non-small cell lung cancer, and esophageal and gastroesophageal junction cancers. Overall survival benefit has been shown in melanoma while survival data are still not mature in other malignancies. Emerging data also show the feasibility of utilizing ICIs in the peri-transplant setting for hepatobiliary malignancies. While ICIs are generally well-tolerated, the development of chronic immune-related adverse events, typically endocrinopathies or neurotoxicities, as well as delayed immune-related adverse events, warrants further scrutiny regarding the optimal duration of adjuvant therapy and requires a thorough risk–benefit determination. The advent of blood-based, dynamic biomarkers such as circulating tumor DNA (ctDNA) can help detect minimal residual disease and identify the subset of patients who would likely benefit from adjuvant treatment. In addition, the characterization of tumor-infiltrating lymphocytes, neutrophil-to-lymphocyte ratio, and ctDNA-adjusted blood tumor mutation burden (bTMB) has also shown promise in predicting response to immunotherapy. Until additional, prospective studies delineate the magnitude of overall survival benefit and validate the use of predictive biomarkers, a tailored, patient-centered approach to adjuvant ICIs that includes extensive patient counseling on potentially irreversible adverse effects should be routinely incorporated into clinical practice.

Cholangiocarcinoma: The Current Status of Surgical Options including Liver Transplantation

“…Despite these promising findings, OLT for iCCA is not currently endorsed as a standard treatment. Nevertheless, ongoing clinical trials seek to establish the utility of OLT for this specific patient group and to identify optimal candidates for this approach [15,22,58,148,149]. When resective surgery of pCCA is considered impractical, OLT can serve as a viable and effective alternative [157].…”

“…These suboptimal results can be attributed to the absence of uniform patient selection criteria and the limited use of neoadjuvant therapies. A significant shift in this landscape emerged when precise patient selection criteria were demonstrated, particularly in enhancing survival outcomes in OLT for early-stage liver cancers [ 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 ]. Therefore, understanding the evolving landscape of surgical treatment options becomes increasingly critical.…”

Transplant Oncology: An Emerging Discipline of Cancer Treatment

“…Although LT in HCC shows promising results, it is only applicable to a small ratio of patients who meet the standards of the Milan criteria. Therefore, neoadjuvant therapies may be useful for downstaging tumors and hindering their progression [123][124][125]. Immune checkpoint inhibitors (ICPIs) have demonstrated significant success in improving outcomes and evolving treatment regimens for a wide range of afflicted patients (Table 2) [126].…”

Editorial: Pathological reactions of cytotoxic lymphoid cells as universal therapeutic targets in cancer and autoimmune disease

“…However, cancer cells operate effective immune evasion machinery, which includes immune checkpoint proteins and small molecular weight compounds as well as biochemical pathways responsible for their expression, production and secretion. These immune evasion networks create an immunosuppressive milieu and allow cancer cells to escape immune attack, thus leading to disease progression ( 1 ).…”