1172P - Analysis of the microbiome of metastatic melanoma patients with complete response to immunotherapy

Background

While immunotherapy has improved the prognosis of metastatic melanoma patients, a minority of patients will have prolonged remission. Recent data have emphasized the role of the gut microbiome in response to immunotherapy; however, there is a discrepancy in defining the optimal microbiome. Although recent fecal microbial transplantation (FMT) trials only included patients with sustained response to immunotherapy, a mixed response was registered, with scarce data on the antimicrobial resistance of the donors. A thorough evaluation of the gut microbiome of potential FMT donors is warranted before future trials.

Methods

A shotgun metagenomic sequencing was performed on Illumina NextSeq 2000 platform on stool samples of metastatic melanoma patients with complete and sustained response to immunotherapy (N=15).

Results

The average age of patients was 61.0 (±12.2) years. Patients usually received immunotherapy in the first line (N=14, 93.3%), with an average time to complete response of 7.6 (± 4.6) months. Firmicutes were the most common phylum with a relative abundance of 62.1% ± 13.2, followed by the Bacteroidetes (31.7% ± 13.8). Protobacteria were present in all patients, ranging from 0.06-3.4%. On Class level, Clostridia were the most abundant (53.9% ± 10.4), followed by Bacteroidia (31.7% ± 13.8). Similar results were seen for the order level, while Lachnospiraceae were the most common family (30.2% ± 8.6) but ranged from 8.1 – 43.8%, followed by Ruminococcaceae (6.7% ± 14.0), and Bacteroidaceae (6.2% ± 11.6). Only 14 bacterial families were present in all patients (25.4%). On the genus level, Bacteroides had the highest relative abundance (11.6% ± 6.2), followed by Lachnospiraceae (10.1% ± 5.9), and Phocaeicola (6.2% ± 4.4). 377 different species were found, with six patients (40%) reporting no traces of the Akkermansia municiphila. Antimicrobial resistance was most commonly found for tetracyclines (63.3% ± 6.9), macrolide-lincosamine-streptogramin B (14.5% ± 7.9), and sulfonamide trimethoprim (4.4% ± 2.4).

Conclusions

Patients with complete and sustained response to immunotherapy exhibit a heterogeneous gut microbiome with common resistance to Tetracycline antibiotics.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Croatian Society of Medical Oncology.

Disclosure

All authors have declared no conflicts of interest.