Clinical outcomes associated with pembrolizumab monotherapy among adults with diffuse malignant peritoneal mesothelioma Journal Article
| Authors: | Marmarelis, M. E.; Wang, X.; Roshkovan, L.; Grady, C. B.; Miura, J. T.; Ginsberg, M. S.; Ciunci, C. A.; Egger, J.; Walker, S.; Cercek, A.; Foote, M. B.; Litzky, L. A.; Nash, G.; Haas, A. R.; Karakousis, G. C.; Cengel, K. A.; Katz, S. I.; Zauderer, M. G.; Langer, C. J.; Offin, M. |
| Article Title: | Clinical outcomes associated with pembrolizumab monotherapy among adults with diffuse malignant peritoneal mesothelioma |
| Abstract: | Importance: Diffuse malignant peritoneal mesothelioma (DMPM) represents a rare and clinically distinct entity among malignant mesotheliomas. Pembrolizumab has activity in diffuse pleural mesothelioma but limited data are available for DMPM; thus, DMPM-specific outcome data are needed. Objective: To evaluate outcomes after the initiation of pembrolizumab monotherapy in the treatment of adults with DMPM. Design, Setting, and Participants: This retrospective cohort study was conducted in 2 tertiary care academic cancer centers (University of Pennsylvania Hospital Abramson Cancer Center and Memorial Sloan Kettering Cancer Center). All patients with DMPM treated between January 1, 2015, and September 1, 2019, were retrospectively identified and followed until January 1, 2021. Statistical analysis was performed between September 2021 and February 2022. Exposures: Pembrolizumab (200 mg or 2 mg/kg every 21 days). Main Outcomes and Measures: Median progression-free survival (PFS) and median overall survival (OS) were assessed using Kaplan-Meier estimates. The best overall response was determined using RECIST (Response Evaluation Criteria in Solid Tumors) criteria, version 1.1. The association of disease characteristics with partial response was evaluated using the Fisher exact test. Results: This study included 24 patients with DMPM who received pembrolizumab monotherapy. Patients had a median age of 62 years (IQR, 52.4-70.6 years); 14 (58.3%) were women, 18 (75.0%) had epithelioid histology, and most (19 [79.2%]) were White. A total of 23 patients (95.8%) received systemic chemotherapy prior to pembrolizumab, and the median number of lines of prior therapy was 2 (range, 0-6 lines). Of the 17 patients who underwent programmed death ligand 1 (PD-L1) testing, 6 (35.3%) had positive tumor PD-L1 expression (range, 1.0%-80.0%). Of the 19 evaluable patients, 4 (21.0%) had a partial response (overall response rate, 21.1% [95% CI, 6.1%-46.6%]), 10 (52.6%) had stable disease, and 5 (26.3%) had progressive disease (5 of 24 patients [20.8%] were lost to follow-up). There was no association between a partial response and the presence of a BAP1 alteration, PD-L1 positivity, or nonepithelioid histology. With a median follow-up of 29.2 (95% CI, 19.3 to not available [NA]) months, the median PFS was 4.9 (95% CI, 2.8-13.3) months and the median OS was 20.9 (95% CI, 10.0 to NA) months from pembrolizumab initiation. Three patients (12.5%) experienced PFS of more than 2 years. Among patients with nonepithelioid vs epithelioid histology, there was a numeric advantage in median PFS (11.5 [95% CI, 2.8 to NA] vs 4.0 [95% CI, 2.8-8.8] months) and median OS (31.8 [95% CI, 8.3 to NA] vs 17.5 [95% CI, 10.0 to NA] months); however, this did not reach statistical significance. Conclusions and Relevance: The results of this retrospective dual-center cohort study of patients with DMPM suggest that pembrolizumab had clinical activity regardless of PD-L1 status or histology, although patients with nonepithelioid histology may have experienced additional clinical benefit. The partial response rate of 21.0% and median OS of 20.9 months in this cohort with 75.0% epithelioid histology warrants further investigation to identify those most likely to respond to immunotherapy. © 2023 American Medical Association. All rights reserved. |
| Keywords: | adult; cancer chemotherapy; clinical article; protein expression; aged; middle aged; retrospective studies; overall survival; histopathology; monotherapy; outcome assessment; follow up; cytoreductive surgery; metabolism; melanoma; progression free survival; cohort studies; peritoneal neoplasms; breast cancer; tumor volume; cohort analysis; pathology; retrospective study; renal cell carcinoma; self report; multicenter study; family history; mesothelioma; cyclin dependent kinase inhibitor 2a; point mutation; protein msh6; peritoneum tumor; programmed death 1 ligand 1; clinical outcome; cyclin dependent kinase inhibitor 2b; overall response rate; response evaluation criteria in solid tumors; high throughput sequencing; humans; human; male; female; article; pembrolizumab; malignant peritoneal mesothelioma; b7-h1 antigen; mesothelioma, malignant; kmt2b gene; ppp1r10 gene |
| Journal Title: | JAMA Network Open |
| Volume: | 6 |
| Issue: | 3 |
| ISSN: | 2574-3805 |
| Publisher: | American Medical Association |
| Date Published: | 2023-03-10 |
| Start Page: | e232526 |
| Language: | English |
| DOI: | 10.1001/jamanetworkopen.2023.2526 |
| PUBMED: | 36897589 |
| PROVIDER: | scopus |
| PMCID: | PMC10942662 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in PubMed and PDF -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work