Journal Article

Immunotherapy for the prevention of high-risk oral disorders malignant transformation: the IMPEDE trial

Lorini, Luigi, Bozzola, Anna, De Cecco, Loris, Serafini, Mara Serena, Paderno, Alberto, Romani, Chiara, Piazza, Cesare, Battocchio, Simonetta, Bignotti, Eliana, Tomasoni, Michele, Miceli, Rosalba, Bardellini, Elena, Majorana, Alessandra, Gurizzan, Cristina, Zigliani, Gabriele, Ardighieri, Laura, Bossi, Paolo, Ravaggi, Antonella

2021

Overview

Background Oral Potentially Malignant Disorders (OPMD) have a non-negligible malignant transformation rate of up to 8%. Loss of heterozygosity (LOH) in critical chromosomal loci has proven to be the most effective marker in defining the risk of transformation and it is found in about 28% of OPMD and may therefore identify patients carrying higher risk. To date, clinical management of OPMD is limited to surgical excision and clinical surveillance, which however do not fully prevent oral cancer development. Immune system has been shown to play a key role in transformation surveillance mechanism and an immunosuppressive imbalance may be responsible for progression to cancer. Given all these considerations, we designed a clinical trial with the aim to prevent OPMD neoplastic transformation and revert the LOH status. Methods This is a phase II, open label, single arm, multicentric trial involving Italian referral centres and expected to enrol 80 patients out of a total of 175 screened. Patients who meet all inclusion criteria and test positive for LOH after an incisional biopsy of the OPMD will undergo a short course of immunotherapy with 4 administration of avelumab. After 6 months since treatment start, resection of the entire OPMD will be performed and LOH assessment will be repeated. The follow-up for malignant transformation and safety assessment will last 30 months from the end of treatment, for a total planned study duration of approximately 5.5 years. Discussion Restoring the activity of immune system through checkpoint inhibitor may play a crucial role against malignant transformation of OPMD by reverting the balance in favour of immune control and preventing cancer occurrence. Trial registration This trial was prospectively registered in ClinicalTrials.gov as NCT04504552 on 7th August 2020.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Antibodies / Autoimmune diseases / Biomedical and Life Sciences / Biomedicine / Biopsy / Cancer Research / Cancer therapies / Cardiovascular disease / Cervix / Disease prevention / Drug dosages / Epidemiology / Genetic transformation / Health Promotion and Disease Prevention / Hepatitis / Heterozygosity / Immune checkpoint / Immune system / Immunotherapy / Informed consent / LOH / Loss of heterozygosity / Malignant transformation / Medicine/Public Health / Monoclonal antibodies / Mouth cancer / Oncology / Oral cancer / Oral potentially malignant disorder / Patients / Prevention / prevention and public health / Risk factors / Study Protocol / Surgical Oncology / Testing / Transplants & implants / Vaccines