Cancer immunotherapy medications do not appear to dramatically worsen the outcomes of cancer patients who develop COVID-19 infection, although many outstanding questions and conflicting data complicate the issue, according to researchers speaking July 20 at the COVID-19 and Cancer Virtual Meeting, presented by the American Association for Cancer Research (AACR).
Research so far has been mixed on a link between immunotherapy and worse outcomes in cancer patients with COVID-19. Some studies suggest that outcomes depend more on the cancer type, when the cancer therapy was started, and factors like the patient’s age and other health problems.
The question about the safety of cancer immunotherapy in the COVID-19 era is critical because many cancer patients take the medications and because there is a theoretical basis to suspect that immunotherapies could worsen COVID-19 outcomes.
Immunotherapies, such as a widely used class of drugs called checkpoint inhibitors (PD-1 inhibitor or CTLA-4 medications) “have become a mainstay of cancer treatment,” says Layne Weatherford, PhD, a postdoctoral fellow at University of Cincinnati in Ohio, who presented data at the AACR session. Studies have also indicated that cancer patients are more prone to developing COVID-19 infection compared with the general population, he says, concluding: “There will continue to be a high number of cancer patients treated with immune checkpoint inhibitors who develop COVID-19.”
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Oncologists Navigate How to Treat Cancer Patients With COVID-19 Infection
Oncologists are struggling to know what to do when a cancer patient on immunotherapy develops a COVID-19 infection, and what to do if a patient is about to begin immunotherapy treatment in a region with high rates of COVID-19, says Muhammad Bilal Abid, MD, an oncologist and assistant professor at the Medical College of Wisconsin in Milwaukee, who has expertise in infectious diseases.
Dr. Abid coauthored a paper as part of the May 20 report in JAMA Oncology highlighting the vexing questions surrounding cancer, COVID-19, and immunotherapy.
“There is considerable concern,” Abid says. “What do we do when the immune system gets revved up after SARS-CoV-2 [the virus that causes COVID-19] and the patient is supposed to start immunotherapy? Do we start immunotherapy now? The dilemma is compounded by the fact that there are no treatment guidelines.”
Doctors are concerned about cancer immunotherapies and COVID-19 because both trigger an immune system reaction. Immunotherapies are drugs that prompt the immune system to respond better to threats from outside invaders, such as cancer cells, viruses, and bacteria, according to the National Cancer Institute (NCI).
Can Immunotherapy and COVID-19 Cause an Overactive Immune System?
Some people with COVID-19 become severely ill due to an overactive immune response called cytokine release syndrome that causes dysfunction in multiple organs and is linked to a higher rate of death, according to research published May 1 in the journal Science.
Cytokine release syndrome is characterized by an overproduction of proteins called cytokines, including an antibody known as IL-6. The theory is that cancer immunotherapy could further increase the immune system reaction that is already overactive due to the COVID-19 infection, says Aljosja Rogiers, PhD, a doctor of internal medicine and a fellow at the Melanoma Institutes Australia.
“Theoretically, checkpoint inhibitors could mitigate or exacerbate COVID-19 infection,” explains Dr. Rogiers.
But his study and others presented at AACR offer some hope that most cancer immunotherapy patients who develop COVID-19 will not suffer undue harm. Rogiers and his colleagues looked at data from 113 cancer patients, about 40 percent of whom were asymptomatic. While they found a higher death rate in cancer patients with COVID-19 (8 percent), older age, other health problems and a more advanced stage of cancer were linked to worse outcomes. Being on cancer immunotherapy was not linked to an increased risk for poor outcomes from COVID-19, according to Rogiers.
Another study presented at AACR and published June 16 in Annals of Oncology examined the outcomes of lung cancer patients in New York City who developed COVID-19. An update to that study found no significant difference in COVID-19 outcomes in patients based on their exposure to PD-1 drugs. As with Rogiers’s study, poor outcomes were linked to older age, other health problems, such as hypertension, and smoking history.
The study should reassure doctors that lung cancer patients can continue to receive cancer treatment according to cancer treatment guidelines, says Jia Luo, MD, a medical oncology fellow at Memorial Sloan Kettering Cancer Center in New York City.
“We should not lose sight that for many of our patients, treating active cancer and delivering the best cancer care remains the primary focus,” says Dr. Luo.
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The Diabetes Drug Metformin May Help
Dr. Weatherford’s study found no evidence of worse outcomes for cancer immunotherapy patients who have COIVD-19. Using blood samples from patients with cancer, his study also examined medications that can calm a cytokine storm and found that the diabetes drug metformin, which is known to dampen IL-6, reduced production of IL-6 in COVID-19 patients.
“These are promising initial findings,” says the study’s senior author, Trisha Wise-Draper, MD, PhD, an associate professor of medicine at the University of Cincinnati College of Medicine and the medical director of the UC Cancer Center clinical trials office.
“Additional research is needed, but our results show that we might be able to treat COVID-19 complications with metformin or a similar drug one day.”
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Clinical Dilemma: COVID-19 and Immune Checkpoint Inhibitors
Additionally, a study published July 1 in the Lancet Oncology from the Teravolt Global Consortium, an international consortium of lung cancer experts who are sharing data on COVID-19 infection, found that neither immune checkpoint inhibitors nor targeted therapies used to treat lung cancer were linked to worse outcomes in patients who develop COVID-19. The study, of more than 400 lung cancer patients, found a death rate of 35 percent but noted that many patients had underlying health problems that likely contributed to death.
“Still,” says one study author, Leora Horn, MD, a thoracic oncologist at Vanderbilt Ingram Cancer Center in Nashville, “cancer and COVID-19 together remain a clinical dilemma. There are conflicting results on the impact of immune checkpoint inhibitors.”
A previous study, published in June in the journal Nature Medicine, found cancer patients who were receiving immunotherapy were at higher risk of severe outcomes and death, particularly people with lung cancer, Dr. Horn noted.
Much more research is needed to address fundamental questions, such as whether it matters when the immunotherapy is started in relation to the COVID-19 diagnosis, Horn and other experts explain.
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Individual Diagnoses, Treatments, and Options Need to Be Discussed
Studies are also looking at cancer type as well as types of immunotherapy. For example, Abid says, a sophisticated type of cancer immunotherapy known as CAR T-cell therapy may be more dangerous to COVID-19 patients. The hyperinflammatory state seen in some cases of COVID-19 infection, he said, is similar to the cytokine release syndrome provoked by CAR T-cell therapy.
Cancer patients should discuss their individual choices with their doctors, taking into account the risk of becoming infected with COVID-19, he suggests. In some cases, immunotherapy could be postponed or stopped in the case of COVID-19 infection.
“This is a difficult time, and difficult decisions are being made,” says Abid. “Patients need all of the information and options.”