Jason Luke, MD, FACP

DISCUSSANT OF the abstract presented by Pinato et al, Jason Luke, MD, FACP, Assistant Professor of Medicine at the University of Chicago Comprehensive Cancer Center, called the survival difference for patients receiving antibiotics prior to checkpoint blockade “rather dramatic and quite impressive,” but he noted that these data raise a number of questions.

“We have to be clear that this was a retrospective analysis, so this antibiosis could in fact be a surrogate for some other poor-risk features that these patients already have,” said Dr. Luke. “In addition, it’s unclear whether 30 days is the appropriate window to examine vs a shorter period of time. It’s possible that a shorter period would have an even more dramatic impact.”

Could Probiotics Augment PD-L1 Response?

AS RESEARCHERS CONTINUE to investigate this issue further, said Dr. Luke, it will be important to distinguish these results from other biomarkers such as tumor mutational burden and programmed cell death ligand 1 (PD-L1) status.

“It’s possible that these patients may not have responded anyway, regardless of prior antibiotic treatment,” said Dr. Luke. “However, these data appear to suggest that the baseline immune state of patients matters with respect to the microbiome. A provocative question might be, should we reestablish the healthy gut microbiome prior to starting checkpoint blockade?”

As Dr. Luke reported, a number of research groups are starting to pursue clinical trials to study the impact of fecal microbiome transfer as well as supplementation of a specific pharmaceutical-grade probiotic to see whether PD-L1 response can be augmented or rescued. ■

DISCLOSURE: Dr. Luke is on the data and safety monitoring board of TTC Oncology; the advisor/consultants for 7 Hills, Actym, Alphamab Oncology, Array, BeneVir, Mavu, Pyxis, Tempest, AbbVie, Aduro, Astellas, AstraZeneca, Bayer, Bristol-Myers Squibb, Castle, CheckMate, Compugen, EMD Serono, Ideaya, Immunocore, Janssen, Jounce, Leap, Merck, Mersana, NewLink, Novartis, RefleXion, Spring Bank, and Vividion; has received institutional research support (unless noted) from AbbVie, Array (scientific research agreement; SRA), Boston Biomedical, Bristol-Myers Squibb, Celldex, CheckMate (SRA), Compugen, Corvus, EMD Serono, Evelo (SRA), Delcath, Five Prime, FLX Bio, Genentech, Immunocore, Incyte, Leap, Medlmmune, Macrogenics, Novartis, Pharmacyclics, Palleon (SRA), Merck, Tesaro, and Xencor; has receivedtravel expenses from Array, AstraZeneca, Bayer, BeneVir, Bristol-Myers Squibb, Castle, CheckMate, EMD Serono, Ideaya, Immunocore, Janssen, Jounce, Merck, Mersana, NewLink, Novartis, and RefleXion; and has patents (both provisional) with Serial #15/612,657 (Cancer Immunotherapy), PCT/US18/36052 (Microbiome Biomarkers for Anti-PD-1/PD-L1 responsiveness: diagnostic, prognostic, and therapeutic uses thereof).