With all the ongoing trials, I have great enthusiasm for the up-and-coming therapeutic options for HNSCC patients with novel agents and combinations in immunotherapy and beyond. —Ravindra Uppaluri, MD, PhD
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October 2020
An earlier study of T-VEC (talimogene laherparepvec, Imlygic), an oncolytic virus, was successfully used in a heart transplant patient with recurrent melanoma. After five therapy cycles, “no evidence of graft rejection has been observed and the patient achieved a complete remission of their melanoma,” noted the study authors (J Immunother Cancer. 2017;5:45).
Looking back, Dr. Uppaluri noted that few would have predicted the wide impact that immunotherapy has achieved in 2020. “With all the ongoing trials, I have great enthusiasm for the up-and-coming therapeutic options for HNSCC patients with novel agents and combinations in immunotherapy and beyond.”
Nikki Kean is a freelance medical writer based in New Jersey.
Where Will Immunotherapy Be in 10 years?
“There are so many exciting frontiers in immunotherapy for HNSCC,” said Ravindra Uppaluri, MD, PhD, director of head and neck surgical oncology at Brigham and Women’s Hospital and Dana-Farber Cancer Institute in Boston. “In 10 years, we’ll likely have a much better understanding of what combination therapeutics are most efficacious, understand what biomarkers can stratify patients for immunotherapy, and further develop novel approaches, including cellular therapies and innate immune targeting.”
Below are two areas of particular interest:
Overcoming Resistance Pathways. PD-1 targeting therapy will remain the “backbone” on which other combinations are built. “In 10 years, I anticipate that the response rate in the R/M first-line and second-line setting can be improved upon, and that immunotherapy will be integrated into the definitive nonsurgical and surgical settings,” said Dr. Uppaluri.
Theodoros N. Teknos, MD, president and scientific director of UH Seidman Cancer Center, in Cleveland, Ohio, agreed that, as “revolutionary” as immunotherapy has been, “overwhelmingly, the majority of patients remain resistant to immune checkpoint inhibition.” That’s why the focus of so much current research has been on overcoming those resistance pathways with either combinations of more than one checkpoint inhibitor or by combining checkpoint inhibitors with T-cell co-stimulating agents, such as anti-OX40 or anti-41BB (a TNF family receptor).
Adoptive T-Cell Transfers. Yet another promising strategy for boosting immune responses involves the use of adoptive T-cell transfers, Dr. Teknos noted. “Scientists are now able to harvest T-cells from a tumor specimen and identify tumor-specific T-cells, expanding them with interleukin-2 and other expansion techniques. The cells are then reinfused into the patient whom they have lympho-depleted.” One study of seven patients has shown that this in fact can be done successfully: the investigators reported a 43% response rate in head and neck cancer patients (Int J Oncol. 2014;45:2051-2057).