Role of immune checkpoint inhibitors in PDL1-negative, low TMB, stable MSI metastatic solid tumours: Single centre study.

Abstract

e14603 Background: Immune check point inhibitors clearly play a part in malignancies with elevated PDL1 expression, high TMB or unstable MSI. There is no information on PDL1 negative, low TMB/MSI stable metastatic solid tumours, however several treatment trials advise using immune check point inhibitors regardless of tissue agnostic indicators. Detailed subset analysis was not performed, though. This study examines the effectiveness of immunotherapy in metastatic solid tumours with PDL1 negative/TMB low/MSI stability. Methods: Study was carried out from Jan-2020 to Dec- 2022 (retrospective data from 2019 also included for analysis). Inclusion criteria: Metastatic solid tumours in patients who received immunotherapy. Exclusion criteria: PDL1>1% ( Either TPS/ CPS >1) by sp263 or 22c3 platforms, TMB> 10, Unstable MSI by IHC or by genomics. Patients who were diagnosed with melanoma, hepatocellular cancer, renal cell carcinoma were also excluded from the study. Response was initially assessed after 3 to 6 cycles of immunotherapy, analysed by PET CT scan. Data were analysed using standard statistical method. Results: After carefully applying exclusion criteria, a total of 40 patients were enrolled in the research, with a male to female ratio of 1.5. Overall response rate in all tumours was 17.5% (7/ 40) Immune checkpoint inhibitors' ORRs at various tumour locations. Among the responders head and neck tumours 2/4 (50%) and lung cancers (37.5%) had higher ORR who also had greater depth of response, living more than 2 years from diagnosis. There is no response observed in gastroesophageal (0/8) gynaecological malignancies (clear cell ovary (0/2), endometrial and cervical (0/3). A patient with urothelial carcinoma who also had a BRCA mutation and was one out of seven responded to IO. Conclusions: Regardless of the presence of PDL1 expression, high TMB, or MSI, adding immune checkpoint inhibitors to the treatment regimen for metastatic head and neck malignancies and lung tumours that lack driver mutations is obviously advantageous. On the other hand, immunotherapy had no effect on gastrointestinal, gynaecological, or urothelial tumours. To validate these findings, more research with several centres and a sizable sample size is necessary. It's interesting that one patient responded to immunotherapy with positive BRCA mutation. Investigating immunotherapy in HRR deficient tumours may shed further insights. [Table: see text]