Academic Journal
Microsatellite Instability, Tumor Mutational Burden, and Response to Immune Checkpoint Blockade in Patients with Prostate Cancer.
| العنوان: | Microsatellite Instability, Tumor Mutational Burden, and Response to Immune Checkpoint Blockade in Patients with Prostate Cancer. |
|---|---|
| المؤلفون: | Lenis, Andrew T, Ravichandran, Vignesh, Brown, Samantha, Alam, Syed M, Katims, Andrew, Truong, Hong, Reisz, Peter A, MD, Vasselman, Samantha, Nweji, Barbara, Autio, Karen A, Morris, Michael J, Slovin, Susan F, Rathkopf, Dana, Danila, Daniel, Scher, Howard I, Woo, Sungmin, Vargas, Hebert Alberto, Laudone, Vincent P, Ehdaie, Behfar, Reuter, Victor, Arcila, Maria, Berger, Michael F, Viale, Agnes, Schultz, Nikolaus, Gopalan, Anuradha, Donoghue, Mark T A, Ostrovnaya, Irina, Stopsack, Konrad H, Solit, David B, Abida, Wassim |
| المصدر: | Department of Medicine |
| بيانات النشر: | LVHN Scholarly Works |
| سنة النشر: | 2024 |
| المجموعة: | Lehigh Valley Health Network: LVHN Scholarly Works |
| مصطلحات موضوعية: | Department of Medicine, Medicine and Health Sciences |
| الوصف: | PURPOSE: Patients with microsatellite instability high/mismatch repair deficient (MSI-H/dMMR) and high tumor mutational burden (TMB-H) prostate cancers are candidates for pembrolizumab. We define the genomic features, clinical course, and response to immune checkpoint blockade (ICB) in patients with MSI-H/dMMR and TMB-H prostate cancers without MSI (TMB-H/MSS). METHODS: We sequenced 3,244 tumors from 2,257 prostate cancer patients. MSI-H/dMMR prostate cancer was defined as MSIsensor score ≥10 or MSIsensor score ≥3 and≥10 mutations/megabase. PSA50 and RECIST responses were assigned. Overall survival (OS) and radiographic progression-free survival (rPFS) were compared using log rank test. RESULTS: 63 (2.8%) men had MSI-H/dMMR and 33 (1.5%) had TMB-H/MSS prostate cancers. Patients with MSI-H/dMMR and TMB-H/MSS tumors more commonly presented with grade group 5 and metastatic disease at diagnosis. MSI-H/dMMR tumors had higher TMB, indel and neoantigen burden compared with TMB-H/MSS. 27 patients with MSI-H/dMMR and 8 patients with TMB-H/MSS tumors received ICB, none of whom harbored POLE mutations. 45% of MSI-H/dMMR patients had a RECIST response and 65% had a PSA50 response. No TMB-H/MSS patient had a RECIST response and 50% had a PSA50 response. rPFS tended to be longer in MSI-H/dMMR patients than in TMB-H/MSS patients who received immunotherapy. Pronounced differences in genomics, TMB or MSIsensor score were not detected between MSI-H/dMMR responders and non-responders. CONCLUSIONS: MSI-H/dMMR prostate cancers have greater TMB, indel and neoantigen burden compared with TMB-H/MSS prostate cancers, and these differences may contribute to more profound and durable responses to ICB. |
| نوع الوثيقة: | text |
| اللغة: | unknown |
| Relation: | https://scholarlyworks.lvhn.org/medicine/6779; https://pubmed.ncbi.nlm.nih.gov/38949888/ |
| الاتاحة: | https://scholarlyworks.lvhn.org/medicine/6779 https://pubmed.ncbi.nlm.nih.gov/38949888/ |
| رقم الانضمام: | edsbas.2D044917 |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |