In the time of COVID-19, there is much to learn about the intersection of coronavirus and cancer. One area of concern has been whether immunotherapies increase the risk of mortality in patients with cancer who also have COVID-19 infection.
“To what extent immune checkpoint inhibition affects COVID-19 infection in patients with cancer is unclear,” said lead author Aljosja Rogiers, MD, a fellow at the Melanoma Institute Australia, Sydney. “Theoretically, inhibition could either mitigate or exacerbate COVID-19 infection. We designed a study to help us answer this question.”
Aljosja Rogiers, MD
According to the results of the multicenter, retrospective analysis presented by Dr. Rogiers,1 treatment with immune checkpoint inhibitors did not increase the risk of mortality in patients with COVID-19 and cancer. The risk of mortality in those receiving immune checkpoint inhibitors was 8%. “This is similar to the mortality rate in the general cancer population [with COVID-19], which is reported to be in the range of 7.6% to 12%,” Dr. Rogiers said, speaking at the 2020 American Association for Cancer Research (AACR) Virtual Meeting: COVID-19 and Cancer.
Of the nine deaths reported in the study, not one was attributable to immune checkpoint inhibitors. All nine patients had advanced cancer, and seven died due to COVID-19–related complications.
The study included 113 patients with cancer who had laboratory-confirmed COVID-19 infection; they received immune checkpoint inhibitors after testing positive for the virus. Patients were treated at 19 centers in North America, Europe, and Australia. The majority (82%) received a PD/1 or PD/L1 inhibitor; 13% received a combination of PD/1 or PD/L1 plus a CTLA-4 inhibitor; and 5% received another immunologic therapy. No patient received chemotherapy.
The median age of patients was 63 years, and 65% were men. Most patients had advanced cancer (74%).
A total of 60% were symptomatic for COVID-19. The most common COVID-19–related symptoms were fever (68%), cough (59%), dyspnea (34%), and myalgia (15%). Comorbidities included cardiovascular (27%), diabetes (15%), pulmonary (12%), and renal (5%). A total of 13% were taking 10 mg or more of prednisone daily.
Of the study patients, 29% were admitted to the hospital for COVID-19 infection. They were treated with antibiotics, oxygen therapy, glucocorticoids, antivirals, intravenous immunoglobulin, and interleukin-6. A total of 5% were admitted to the intensive care unit, where 3% received mechanical ventilation and 2%, vasopressin. A total of 61% of patients were discharged from the hospital, 12% remained in the hospital, and 27% of those admitted to the hospital (n = 9) died by the time of data cutoff.
“It appeared there was a slightly higher rate of COVID-19 mortality in patients with non–small cell lung cancer than with melanoma,” Dr. Rogiers said.
Effect of Immune Checkpoint Inhibitor Remains Unclear
Looking at data from the TERAVOLT registry (patients with thoracic cancers and COVID-19 infection) as well as data on 218 patients with cancer treated at a single institution, Leora Horn, MD, Clinical Director Thoracic Oncology Program, Vanderbilt-Ingram Cancer Center, Nashville, and one of the leaders in the TERAVOLT registry,
Leora Horn, MD
commented: “It is clear that patients with cancer are at increased mortality from COVID-19 infection compared with the general population. Patients with lung and hematologic cancers appear to be at particularly high risk. It is unclear which therapy is associated with worsening survival, but chemotherapy and maybe immunotherapy are.”
Dr. Horn acknowledged a number of limitations to the available data on immune checkpoint inhibitors in patients with cancer who have COVID-19 infection. “These studies include different endpoints, no data on whether the timing of initiation of immune checkpoint inhibitor matters, unclear data on presenting symptoms, unclear data on the time of COVID-19 infection relative to the pandemic in a given city or country, no clear data on therapies given for COVID-19 infection and their impact on outcomes, no data on whether it matters whether immune checkpoint inhibitors are given alone or in combination with another therapy, and no data on the impact of an adverse event on prior immune checkpoint inhibitor beyond pneumonitis,” she noted.
“The question of whether immune checkpoint inhibitors and other immunotherapies worsen outcomes in patients who have cancer and COVID-19 infection is being studied. Data so far suggest they likely do not fare worse than other patients with cancer, and they may even do better,” said David Tuveson, MD, AACR President-Elect and Program Chair for the AACR Virtual Meeting: COVID-19 and Cancer. Dr. Tuveson is also Director of the Cancer Center at Cold Spring Harbor Laboratory, Cold Spring Harbor, New York.
David Tuveson, MD
“Many patients are on immunotherapy for melanoma and lung cancer, and immune checkpoint inhibitors activate T cells. These patients are not immunosuppressed; they are immune-ambivalent due to the fact that they have cancer. We are trying to create an autoimmune disease that attacks the cancer cells with immune checkpoint inhibitors,” Dr. Tuveson continued.
“We haven’t seen a major deleterious effect when patients on immune checkpoint inhibitors contract COVID-19,” he added. “We do know that patients with lung cancer are more severely affected. The question is, do they get better if they are on immune checkpoint inhibitors? No one has done that study, but speakers at the meeting presented data suggesting that immunity to the virus is low. It may turn out that people on immune checkpoint inhibitors do better.”
DISCLOSURE: Dr. Rogiers reported no conflicts of interest. Dr. Horn has served as a consultant or advisor to Amgen, AstraZeneca, Bayer, EMD Serono, Genentech, Incyte, Merck, Pfizer, Tesaro, and Xcovery; has received institutional research funding from Boehringer Ingelheim and Xcovery; and has been reimbursed for travel, accommodations, or other expenses by Xcovery. Dr. Tuveson reported financial relationships with Surface Oncology, Ono Pharmaceutical, Merck, Leap Therapeutics, FibroGen, Cygnal, Chugai, and Mestag Therapeutics.
1. Rogiers A, Tondini C, Grimes JM, et al: Clinical characteristics and outcomes of coronavirus 2019 disease (COVID-19) in cancer patients treated with immune checkpoint inhibitors. 2020 AACR Virtual Meeting: COVID-19 and Cancer. Symposium 2.