P864 Combination of fecal microbiota transplantation from healthy donors with anti-PD1 immunotherapy in treatment-naïve advanced or metastatic melanoma patients
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Résumé
<h3>Background</h3> Checkpoint inhibitors have changed the outcomes for patients with advanced melanoma. However, many patients still show primary resistance to single-agent therapy. Recently, the role of the gut microbiome in influencing antitumor immunity has been established. Currently, various methods of modifying the gut microbiome of cancer patients are being explored. We report the initial safety results of the first two patients treated on a phase I study combining Fecal Microbiota Transplantation (FMT) with single-agent anti-PD1 in treatment-naïve patients with advanced melanoma. <h3>Methods</h3> Two healthy donors were selected through our screening process and approximately 100 grams of fresh stool was processed and prepared for FMT as per our standardized protocol. FMT recipients were melanoma patients with unresectable or metastatic disease who were treatment naïve for their advanced disease. Bowel preparation was completed the day prior and FMT was performed using oral administration of approximately 40 capsules. Anti-PD1 was started at least 1 week after FMT to allow for microbiome engraftment. Blood and stool were analyzed at baseline (pre-FMT), before immunotherapy, and three weeks after it. <h3>Results</h3> Patient 1 was diagnosed with recurrent melanoma of the lower limb with multiple in-transit lesions refractory to control with surgery and a single intralesional injection of IL-2. Patient received stool from Donor 1 and did not experience any adverse effects from FMT. At the time of treatment #4, a solitary large cutaneous lesion stabilized but the patient experienced grade 1 diarrhoea, grade 2 nausea, and grade 2 fatigue, and grade 2 depression (NCI-CTCAE v5.0). Patient 2 was diagnosed with recurrent melanoma of the parotid gland with metastatic lesions in the lungs. Patient 2 received stool from Donor 2 and experienced only grade 1 flatus from FMT. At the time of treatment #3, the patient experienced grade 1 constipation. Both patients had a vigorous immune response to FMT measured by changes in the immune subpopulations in peripheral blood one week after FMT, including an increase in CD28+ CD8+ T cells and a decrease in PDL1+ CD3- cells. Following anti-PD1 therapy, both patients had an increase in CD39+ CD8+ T cell population. The PD1+ CD38+ CD8+ dysfunctional T cell levels decreased in both patients post-FMT and anti-PD1 therapy. <h3>Conclusions</h3> FMT combined with anti-PD1 therapy in patients with advanced melanoma appears to be safe. A measurable immune response was observed one week after FMT in both patients. One patient experienced several grade 2 toxicities with stabilization of a large cutaneous lesion. <h3>Acknowledgements</h3> This study is funded by a grant from The Lotte & John Hecht Memorial Foundation and a grant from The Medical Oncology Research Funds (MORF) from Western University. <h3>Trial Registration</h3> NCT03772899 <h3>Ethics Approval</h3> The study was approved by Western University Institutution‘s Ethics Board, approval number 113131, date of approval March 15, 2019.
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Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découle