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The Promise of Cancer Immunotherapy: Why Patient Education Is Critical, Part I

Debra Madden is a 2-time cancer survivor who was diagnosed with Hodgkin's lymphoma as a young adult and breast cancer nearly 20 years later, which was thought to be secondary to the radiation she had received for her original cancer treatment. Debra became an active Cancer Research Advocate following her second cancer diagnosis at the age of 42 years. She is currently a member of the ECOG/ACRIN Cancer Research Group and the Patient-Centered Outcomes Research Institute's Advisory Panel on the Assessment of Prevention, Diagnosis, and Treatment Options. She also serves on multiple grant review panels, including the Congressionally Directed Medical Research Program Breast Cancer Research Program. Debra blogs at "Musings of a Cancer Research Advocate", ( and you can follow her on Twitter at @AdvocateDebM.
In recent years, cancer immunotherapy has emerged as one of the most promising breakthroughs in treating multiple cancer types. The media is filled with reports on blockbuster immunotherapy results, describing it as the most exciting development in cancer therapies in decades—particularly when contrasted with the many agents approved by the FDA based on small effects, increasing survival by weeks or perhaps months when compared with standard treatments for patients with advanced cancers.

Immunotherapy has understandably been a primary focus of discussion among researchers, clinicians, patient advocates, payers, and other stakeholders at major research conferences and meetings during the past few years, including the annual meetings of the American Society of Clinical Oncology (ASCO) and the American Association for Cancer Research (AACR). Further, there has been a proliferation of immunotherapy-specific conferences, including last year’s coordinated efforts by AACR, the Cancer Research Institute, the Association for Cancer Immunotherapy, and the European Academy of Tumor Immunology to sponsor the first International Cancer Immunotherapy Conference. The explosion of interest in this new class of therapies has made the research and development of novel immunotherapies an extremely active field, and some patients with advanced, difficult-to-treat cancers, such as malignant melanomas and lung cancers, are finding hope that such agents may successfully treat or make a meaningful difference in the ability to fight their cancers. In fact, ASCO recently designated immunotherapy as the Top Cancer Advance of the Year in its “Clinical Cancer Advances 2016: ASCO’s Annual Report on Progress Against Cancer,”1 noting that “The continued wave of success with immunotherapies, which has extended beyond just a few tumor types, promises to transform cancer care.”
Immunotherapy is considered promising due to multiple factors:
  • It is systemic therapy.
  • It enhances the immune system’s innate ability to recognize and fight cancer cells.
  • It increases specificity in unleashing the immune system’s ability to recognize, target, and selectively kill cancer cells.
  • It has the ability to “remember” specific cancer antigens, which may lead to durability of response and longer term protection.
  • It has the potential to treat multiple traditionally difficult-to-treat cancer types.
Checkpoint Inhibitors

Much of the excitement has focused on novel agents called checkpoint inhibitors, which unleash an immune attack directed against cancer cells. The immune system has several checkpoint pathways or “negative regulators” that serve to put the brakes on over-activation of the immune system in normal, healthy tissue. The T cells of the immune system are on constant patrol, seeking signs of infection or disease. Upon encountering other cells, they seek to identify the cell by probing specific proteins on its surface. If the proteins suggest that the cell is infected, cancerous, or toxic, the T cells will mount an attack, and the immune system then begins to increase its immune checkpoint molecules to prevent the attack from harming the body’s healthy tissues. Many cancer cells have the ability to exploit these checkpoint pathways (eg, CTLA-4 and PD-1/PD-L1 pathways), up-regulating the inhibitory immune pathways and blocking or deactivating the immune cells, such that the T cells are unable to recognize the cancerous cells as invading threats, enabling them to grow and proliferate out of control.
The checkpoint inhibitors are designed to release these brakes on the immune system by inhibiting the checkpoint, enabling T cells to mount a more effective attack against cancer cells.

To date, 3 checkpoint inhibitors have received accelerated approval by the FDA, including ipilimumab (Yervoy), nivolumab (Opdivo), and pembrolizumab (Keytruda) based on durable responses in patients with advanced non-small-cell lung cancer (nivolumab, pembrolizumab), malignant melanoma (nivolumab, pembrolizumab, ipilimumab [with the latter also approved for stage III melanoma]), and metastatic renal cancer (nivolumab) resistant to other available treatments. For drugs that receive accelerated approval from the FDA, sponsors are required to conduct studies to confirm the anticipated clinical benefit—where the drug will be granted traditional approval if the confirmatory trial results show clinical benefit, or the drug (or the specific indication) may be removed from the market if the confirmatory trial does not demonstrate clinical benefit.

Adoptive T-Cell Therapy

Recent headlines also pronounced that dramatic remissions were reported by immunotherapy researcher and Fred Hutchinson Cancer Research Center oncologist, Stanley Riddell, MD, during this year’s annual meeting of the American Association for the Advancement of Science (AAAS), where he announced extraordinary results in early trials using adoptive T-cell therapy, noting that “The early data is unprecedented.”  For such personalized therapy, T cells were obtained from cancer patients, genetically modified and tagged with receptor molecules to help them target specific cancer cells, and then administered back to the patients to boost the immune system’s ability to fight the cancerous cells. Riddell reported that in one study with heavily pretreated patients with advanced blood cancers, treatment eliminated symptoms in 94% of patients with acute lymphoblastic leukemia, patients with other blood cancers had response rates greater than 80%, and more than 50% of patients demonstrated complete remission. Yet severe immune responses developed in 7 patients, resulting in 2 deaths. Riddell said, “There are reasons to be optimistic, there are reasons to be pessimistic,” adding that he and his colleagues believe lowering the T-cell dose may help to reduce the risk of adverse effects. Because the research has not yet been published nor peer reviewed, the results are currently difficult to evaluate.2,3

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