2018 was a big year for cancer immunotherapy, with several approvals in new cancer types as well as a number of promising breakthroughs with the potential to dramatically improve how patients are treated in the future.
To recap the highlights of the past year and discuss what’s next in cancer immunotherapy, the Cancer Research Institute (CRI) hosted a webinar for patients and caregivers with Elizabeth M. Jaffee, M.D., who currently serves as a member of the CRI Scientific Advisory Council, president of the American Association for Cancer Research (AACR), and deputy director of the Sidney Kimmel Comprehensive Cancer Center as well as the associate director of the Bloomberg~Kimmel Institute for Cancer Immunotherapy at Johns Hopkins University in Baltimore, MD, among other positions.
In this webinar, which you can watch in full, Dr. Jaffee primarily highlighted the following areas:
New Immunotherapy Approvals
In 2018, the U.S. Food and Drug Administration (FDA) approved checkpoint immunotherapies targeting the PD-1/PD-L1 pathway for several new populations of cancer patients. Starting in February, durvalumab was approved for patients with stage III non-small cell lung cancer (NSCLC), the most common type of lung cancer. Previously, checkpoint immunotherapies were only approved for patients with more advanced, metastatic NSCLC. In June, pembrolizumab was approved to treat advanced cervical cancer; in August, nivolumab was approved to treat metastatic small cell lung cancer (SCLC); and in September, cemiplimab was approved for patients with cutaneous squamous cell carcinoma (CSCC), the second most common skin cancer and the deadliest non-melanoma skin cancer. Each of these immunotherapies became the first to be approved by the FDA for these respective patient populations.
Additionally, several combination treatments involving checkpoint immunotherapy were approved in 2018 as first-line options, meaning that patients can now receive them following their initial diagnosis. In April, the combination of nivolumab and ipilimumab—checkpoint immunotherapies that target the PD-1 and CTLA-4 pathways, respectively—was approved for first-line treatment of renal cell carcinoma (RCC), the most common form of kidney cancer, whereas there were two different combinations—pembrolizumab (anti-PD-1) plus chemotherapy as well as atezolizumab (anti-PD-L1) plus bevacizumab, a VEGF-targeting antibody—approved for first-line treatment of patients with metastatic NSCLC.
Lastly, while it’s still being evaluated in clinical trials and is not yet approved by the FDA, another promising advance in the context of treating patients with immunotherapy earlier in the course of treatment was highlighted by CRI-SU2C Dream Team investigator Drew Pardoll, M.D., Ph.D., a colleague of Jaffee’s at Johns Hopkins. Pardoll’s study revealed that when patients with early stage (stage 1-3) NSCLC were treated with anti-PD-1 immunotherapy prior to surgery, nearly half of them experienced “major pathologic responses” that have historically been associated with long-term survival.
Immunotherapy Combinations for Hard-to-Treat Cancers
Next, Jaffee focused on breakthroughs involving immunotherapy combinations that appeared promising against hard-to-treat cancer types. The combination of anti-PD-L1 checkpoint immunotherapy plus chemotherapy demonstrated benefit as a first-line treatment in a trial for patients with advanced triple-negative breast cancer. In another trial, promising results were observed in triple-negative breast cancer and ovarian cancer patients, particularly those who possessed the BRCA mutation, when anti-PD-1 immunotherapy was combined with PARP inhibition, which can prevent cancer cells from being able to repair their DNA.
Biomarkers in Immunotherapy
In addition to biomarkers such as MSI/dMMR and BRCA, Dr. Jaffee discussed how our understanding of biomarkers has evolved in the last year and how subsequent advances could improve clinical care for patients even further. Specifically, she spoke about three different “groups” of biomarkers. The first included PD-L1 expression, the presence of tumor-infiltrating immune cells, and tumor mutational burden, which together can provide insights into whether a tumor is “hot” and likely immunotherapy-responsive, or “cold” and likely resistant to immunotherapy. The second dealt with other signaling pathways in the tumor microenvironment (TME) that can shut down immune responses and how these might be able to be turned into biomarkers to guide treatment using newer immunotherapies. The third focused on the gut microbiome, which includes the trillions of bacteria that reside in our intestines. Recently, the field has come to appreciate that these bacteria—and factors like antibiotics that affect these bacteria—can influence how patients respond to immunotherapy treatment. As a result, proactive strategies to beneficially modulate patients’ microbiomes are now being explored in clinical trials.
Immunotherapies that utilize patients’ own immune cells are another important immune-based approach. In addition to discussing how these strategies, including CAR T cells, are being made safer and more effective against blood cancer, where they’ve already made an incredible impact in the clinic, Jaffee focused on efforts to develop off-the-shelf sources of cancer-fighting immune cells to ensure patients can be treated in a timelier and more cost-effective fashion. Furthermore, she discussed how this innovative and powerful cellular approach is now being applied to patients with solid cancers, including one strategy highlighted by the National Cancer Institute’s Steven A. Rosenberg, M.D., Ph.D., that engineers T cells to target the unique, patient-specific mutations found in an individual’s tumors.
Personalizing Immunotherapy with Vaccines
One of the most promising features of utilizing the immune system against cancer is the ability to personalize treatments for individual patients, each of whom have tumors with different sets of mutations. To that end, Dr. Jaffee highlighted several vaccine approaches designed to stimulate immune responses against cancer-specific targets. Early studies have thus far shown promise in melanoma, glioblastoma, and HPV-associated cancers.
The Future: Technology, Translational Research, and Collaborations
Finally, Jaffee shared with us her vision of the future of cancer immunotherapy, which will, in part, be enabled by the contributions of the Cancer Research Institute (CRI). She specifically mentioned three areas that are important when it comes to fueling the field’s progress. First, better tools and technologies are enabling doctors and scientists to better understand the relationship between a tumor and the immune system (such as the cancer-on-a-chip being developed by CRI Tech Impact Award recipient Dan (Dongeun) Huh, Ph.D., of the University of Pennsylvania). Second, more innovative clinical trial design (à la CRI’s Clinical Accelerator efforts). Third, the importance of collaborations between nonprofit, academic, and biotechnology/pharmaceutical industry partners, all of whom are important for ensuring that new and improved treatments and discovered and brought into the clinic for patients, because “not one group can do this on their own.”
Elizabeth M. Jaffee, M.D., currently works at Johns Hopkins University in Baltimore, where she holds many prestigious positions, including serving as the deputy director of the Sidney Kimmel Comprehensive Cancer Center, the associate director of the Bloomberg~Kimmel Institute for Cancer Immunotherapy, the Dana and Albert “Cubby” Broccoli professor of oncology, co-director of gastrointestinal cancer and diseases program, and co-director of the Skip Viragh Center for Pancreas Cancer Clinical Research and Patient Care.
Outside of Johns Hopkins, Dr. Jaffee also currently serves as the chair of the National Cancer Advisory Board for the National Cancer Institute, the co-chair of the National Cancer Institute Blue Ribbon Panel for the National Cancer Moonshot Initiative, the leader of the Stand Up To Cancer-Lustgarten Foundation Pancreatic Cancer Dream Team, and the president of the American Association for Cancer Research, among other roles. Dr. Jaffee has received numerous awards in recognition of her contributions, including the AACR Joseph H. Burchenal Memorial Award for Outstanding Achievement in Clinical Cancer Research in 2015 and the Johns Hopkins University Office of Women in Science and Medicine Vice Dean’s Award in 2012. Dr. Jaffee is also a member of the Cancer Research Institute Scientific Advisory Council.
This webinar, the first in the 2019 Cancer Immunotherapy and You webinar series, is made possible with generous support from Bristol Myers-Squibb as well as Cellectis.