Article
Hematology
Matthew Mei, Lu Chen, James Godfrey, Joo Song, Colt Egelston, Sandrine Puverel, Elizabeth Budde, Saro Armenian, Liana Nikolaenko, Mary Nwangwu, Weihua Guo, Lei Gao, Peter Lee, Robert Chen, Shari Daniels, Neena Kennedy, Lacolle Peters, Jasmine Zain, Steven Rosen, Stephen Forman, Leslie Popplewell, Larry Kwak, Alex F. Herrera
Summary: This phase 1 study evaluated the addition of vorinostat to pembrolizumab in patients with follicular lymphoma. The study found that the combination therapy had a high overall response rate in patients with relapsed classical Hodgkin's lymphoma.
Article
Oncology
Luke Frankiw, Arun Singh, Cole Peters, Begona Comin-Anduix, Beata Berent-Maoz, Mignonette Macabali, Kiana Shammaie, Crystal Quiros, Paula Kaplan-Lefko, Ignacio Baselga Carretero, Antoni Ribas, Theodore Scott Nowicki
Summary: In this study, a new mechanism of treatment resistance in sarcoma involving loss of NY-ESO-1 expression after transgenic adoptive cell therapy with dendritic cell vaccination and PD-1 blockade was described. Initial tumor regression was observed, but tumor progression and loss of NY-ESO-1 expression were found later. This study provides insights for improving cellular therapy.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Oncology
Julie Delyon, Lucie Biard, Marion Renaud, Matthieu Resche-Rigon, Jerome Le Goff, Stephane Dalle, Valentine Heidelberger, Laetitia Da Meda, Laurie Toullec, Guislaine Carcelain, Samia Mourah, Sophie Caillat-Zucman, Vincent Allain, Maxime Battistella, Celeste Lebbe
Summary: PD-1 blockade with pembrolizumab shows promising anti-tumor activity and acceptable safety profile in patients with classic and endemic Kaposi sarcoma.
Editorial Material
Oncology
Cedric Rossi, Rene-Olivier Casasnovas
Summary: Novel targeted approaches have significantly improved the prognosis of patients with relapsed/refractory Hodgkin lymphoma, especially with the use of inhibitors like Nivolumab and pembrolizumab.
EUROPEAN JOURNAL OF CANCER
(2022)
Article
Multidisciplinary Sciences
Emily R. Webb, Julia Moreno-Vincente, Alistair Easton, Silvia Lanati, Martin Taylor, Sonya James, Emily L. Williams, Vikki English, Chris Penfold, Stephen A. Beers, Juliet C. Gray
Summary: This study investigated the immunomodulatory effects of low-dose cyclophosphamide (CPM) and found that CPM can specifically deplete intratumoral T regulatory cells through apoptosis. When combined with anti-PD-1 antibody therapy, therapeutic efficacy is improved. These findings strongly support clinical evaluation of such combination strategies in neuroblastoma.
Article
Hematology
Pamela B. Allen, Xinyan Lu, Qing Chen, Kaitlyn O'Shea, Joan S. Chmiel, Liron Barnea Slonim, Madina Sukhanova, Hatice Savas, Andrew M. Evens, Ranjana Advani, Barbara Pro, Reem Karmali, Brett Palmer, Robert A. Bayer, Robert M. Eisner, Eric Mou, Gary Dillehay, Leo I. Gordon, Jane N. Winter
Summary: In this study, nearly two-thirds of patients with untreated, unfavorable, or advanced-stage classic Hodgkin lymphoma achieved complete or near-complete metabolic responses (CMRs) after pembrolizumab monotherapy. All patients achieved CMR after 2 cycles of AVD chemotherapy, and the progression-free survival and overall survival remained 100% after a median follow-up of 33.1 months. The high response rates suggest that even low levels of PD-L1 expression are sufficient for response to PD-1 blockade in untreated cHL.
Article
Medicine, General & Internal
Sapna P. Patel, Megan Othus, Yuanbin Chen, G. Paul Wright, Kathleen J. Yost, John R. Hyngstrom, Siwen Hu-Lieskovan, Christopher D. Lao, Leslie A. Fecher, Thach-Giao Truong, Jennifer L. Eisenstein, Sunandana Chandra, Jeffrey A. Sosman, Kari L. Kendra, Richard C. Wu, Craig E. Devoe, Gary B. Deutsch, Aparna Hegde, Maya Khalil, Ankit Mangla, Amy M. Reese, Merrick I. Ross, Andrew S. Poklepovic, Giao Q. Phan, Adedayo A. Onitilo, Demet G. Yasar, Benjamin C. Powers, Gary C. Doolittle, Gino K. In, Niels Kokot, Geoffrey T. Gibney, Michael B. Atkins, Montaser Shaheen, James A. Warneke, Alexandra Ikeguchi, Jose E. Najera, Bartosz Chmielowski, Joseph G. Crompton, Justin D. Floyd, Eddy Hsueh, Kim A. Margolin, Warren A. Chow, Kenneth F. Grossmann, Eliana Dietrich, Victor G. Prieto, Michael C. Lowe, Elizabeth I. Buchbinder, John M. Kirkwood, Larissa Korde, James Moon, Elad Sharon, Vernon K. Sondak, Antoni Ribas
Summary: This study aimed to investigate whether giving pembrolizumab both before and after surgery would improve event-free survival in patients with resectable stage III or IV melanoma. Results showed that patients who received pembrolizumab both before and after surgery had significantly longer event-free survival. Overall rating: 9 out of 10.
NEW ENGLAND JOURNAL OF MEDICINE
(2023)
Article
Oncology
Hikmat H. Assi, Chihunt Wong, Kimberly A. Tipton, Li Mei, Ken Wong, Jennifer Razo, Chanty Chan, Bruce Howng, Jason Sagert, Michael Krimm, Linnea Diep, Andrew Jang, Margaret T. Nguyen, Nicole Lapuyade, Victoria Singson, Ruth Villanueva, Madan Paidhungat, Shouchun Liu, Vangipuram Rangan, Olga Vasiljeva, James W. West, Jennifer H. Richardson, Bryan Irving, Dylan Daniel, Marcia Belvin, W. Michael Kavanaugh
Summary: Using protease-activatable antibody prodrugs (Pb-Tx) to locally inhibit PD-1/PD-L1 can reduce systemic immune toxicity while eliciting potent anti-tumor immune responses.
CANCER IMMUNOLOGY RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Farshad Nassiri, Vikas Patil, Leeor S. Yefet, Olivia Singh, Jeff Liu, Rachel M. A. Dang, Takafumi N. Yamaguchi, Mariza Daras, Timothy F. Cloughesy, Howard Colman, Priya U. Kumthekar, Clark C. Chen, Robert Aiken, Morris D. Groves, Shirley S. Ong, Rohan Ramakrishna, Michael A. Vogelbaum, Simon Khagi, Thomas Kaley, Jason M. Melear, David M. Peereboom, Analiz Rodriguez, Maxim Yankelevich, Suresh G. Nair, Vinay K. Puduvalli, Kenneth Aldape, Andrew Gao, Alvaro Lopez-Janeiro, Carlos E. de Andrea, Marta M. Alonso, Paul Boutros, Joan Robbins, Warren P. Mason, Adam M. Sonabend, Roger Stupp, Juan Fueyo, Candelaria Gomez-Manzano, Frederick F. Lang, Gelareh Zadeh
Summary: Immune-mediated anti-tumoral responses, elicited by oncolytic viruses and augmented with checkpoint inhibition, were evaluated in a multicenter phase 1/2 study for the treatment of recurrent glioblastoma. The combination of intratumoral DNX-2401 followed by intravenous pembrolizumab showed notable survival benefit with an objective response rate of 10.4% and overall survival at 12 months of 52.7%. Exploratory analyses suggested potential predictors of treatment response and resistance. Overall, this combination therapy demonstrated promising results in select patients with glioblastoma.
Article
Oncology
Hyun Ae Jung, Sehhoon Park, Yoon-La Choi, Se-Hoon Lee, Jin Seok Ahn, Myung-Ju Ahn, Jong-Mu Sun
Summary: This study found that continuing pembrolizumab with chemotherapy did not improve survival in patients with non-small cell lung cancer (NSCLC) who had previously failed PD-1/PD-L1 inhibitor therapy. However, in a subgroup with high expression of PD-L1 in tumor cells and favorable clinical outcomes to prior PD-1/PD-L1 inhibitor, the pembrolizumab-chemotherapy arm showed a higher 24-month survival rate.
CLINICAL CANCER RESEARCH
(2022)
Review
Oncology
Xiaoxiang Zhou, Zhuoran Yao, Hua Bai, Jianchun Duan, Zhijie Wang, Xin Wang, Xue Zhang, Jiachen Xu, Kailun Fei, Zhen Zhang, Fengwei Tan, Qi Xue, Shugeng Gao, Yibo Gao, Jie Wang, Jie He
Summary: This study comprehensively investigated the incidences and profiles of treatment-related adverse events in different PD-1 or PD-L1 inhibitor-based combination therapies. Results showed variations in the incidence and profiles of adverse events among different combination therapies, providing essential reference for clinicians in routine practice of cancer care.
Editorial Material
Oncology
Lilit Karapetyan, Jason J. Luke
Summary: Targeting coinhibitory receptors on dysfunctional T cells may improve response to anti-PD-(L)1 in the IFNy associated T-cell-inflamed tumor microenvironment. The bispecific lymphocyte activation gene 3 (LAG-3) and PD-L1 blocking antibody FS118, potentially through LAG-3 shedding, represents a promising strategy to improve immune checkpoint blockade. Soluble LAG-3 is an intriguing biomarker for LAG-3 drug activity.
CLINICAL CANCER RESEARCH
(2023)
Article
Oncology
Martin Reck, Delvys Rodriguez-Abreu, Andrew G. Robinson, Rina Hui, Tibor Csoszi, Andrea Fulop, Maya Gottfried, Nir Peled, Ali Tafreshi, Sinead Cuffe, Mary O'Brien, Suman Rao, Katsuyuki Hotta, Ticiana A. Leal, Jonathan W. Riess, Erin Jensen, Bin Zhao, M. Catherine Pietanza, Julie R. Brahmer
Summary: This study reports the first 5-year follow-up of a first-line immunotherapy trial for NSCLC, demonstrating that pembrolizumab provides a durable, clinically meaningful long-term overall survival benefit in first-line treatment of metastatic NSCLC with a PD-L1 tumor proportion score of at least 50%.
JOURNAL OF CLINICAL ONCOLOGY
(2021)
Article
Multidisciplinary Sciences
Changsheng Huang, Shengxiang Ren, Yaqi Chen, Anyi Liu, Qi Wu, Tao Jiang, Panjing Lv, Da Song, Fuqing Hu, Jingqing Lan, Li Sun, Xue Zheng, Xuelai Luo, Qian Chu, Keyi Jia, Yan Li, Jun Wang, Caicun Zou, Junbo Hu, Guihua Wang
Summary: This research discovered that PD-L1 K162 was methylated by SETD7 and demethylated by LSD2. Additionally, PD-L1 K162 methylation controlled the PD1/PD-L1 interaction and significantly enhanced the suppression of T cell activity in controlling cancer immune surveillance. The study demonstrated that PD-L1 hypermethylation was the key mechanism for anti-PD-L1 therapy resistance, identified PD-L1 K162 methylation as a negative predictive marker for anti-PD-1 treatment in patients with non-small cell lung cancer, and showed that the PD-L1 K162 methylation:PD-L1 ratio was a more accurate biomarker for predicting anti-PD-(L)1 therapy sensitivity.
Editorial Material
Oncology
James W. Smithy, Jason J. Luke
Summary: A retrospective analysis revealed that higher pretreatment tissue densities of CD16(+) macrophages were correlated with clinical benefit from combined CTLA-4 and PD-1 blockade in patients with unresectable melanoma. This biomarker could potentially be used in selecting immune checkpoint inhibitor regimens with further validation.
CLINICAL CANCER RESEARCH
(2023)
