Recommendations for Immune-Engaging Therapies During the COVID-19 Pandemic

In an article published in JAMA Oncology, researchers discussed recommendations for patients who develop coronavirus disease 2019 (COVID-19) while receiving immunotherapy or other advanced immune-engaging therapies. 

Though conventional cancer treatments, such as chemotherapy and radiation, directly damage both normal and cancerous cells, immune-engaging therapies utilize the patients’ own immune systems to specifically target tumor cells. 

“Conventional immune checkpoint inhibitors (ICIs), such as programmed cell death 1 and cytotoxic T-lymphocyte antigen 4 inhibitors, restore the tumor immunosurveillance and revivify the immune system to target the tumor cells,” the authors wrote. “Hence, ICI works by bolstering the immune system, which may result in autoimmunity.”

Though a lot remains to be discovered in regard to COVID-19, the preliminary immunological understanding of risk factors associated with acute respiratory distress syndrome (ARDS) and mortality COVID-19 suggests that ICI-associated pneumonitis may further exacerbate pulmonary inflammation. 

Given this knowledge, the researchers recommended that patients receiving ICI who develop any respiratory system or who have had contact with a patient with COVID-19 should be tested for COVID-19. Additionally, patients who are diagnosed with COVID-19 who are not critically ill should have their ICI postponed until complete resolution of infection or wait for at least 2 weeks, whichever comes later. 

For those receiving ICI who develop critical illness due to COVID-19, researchers indicated that immunosuppressive therapy should be considered in addition to immediate cessation of ICI.

“A retrospective multicenter study from China including 150 patients (with laboratory-confirmed infection of COVID-19) showed that C-reactive protein and interleukin-6 levels were considerably higher in the 68 patients (45.3%) who died in comparison with the 82 patients (54.6%) who were discharged healthy,” the authors wrote. “Hence, the potential therapeutic armamentarium for COVID-19-associated ARDS could be similar to that used to treat CRS associated with CAR T-cells. These may include granulocyte-macrophage colony-stimulating factor inhibition, targeted cytokine blockade such as interleukin-1 (anakinra), interleukin 6 (tocilizumab, siltuximab, and sarilumab), and Janus kinase inhibition.”

Researchers indicated that randomized clinical trials with exploratory arms are critically necessary in this space, with some already underway.

Similarly, it was recommended that any patient diagnosed with COVID-19, whether with mild flu-like symptoms or ARDS, should not be administered any form of CAR T-cells. Comparable to circumstances in the ICI setting, once a patient is fully recovered from COVID-19 and remains well for at least 2 weeks after recovery, the researchers indicated that patients may be considered eligible to undergo further CAR T-cell therapy. 

However, extreme caution should still be exercised with bispecific T-cell engagers, (eg, blinatumomab), tumor-infiltrating lymphocytes, and other advanced immune-engaging therapies, such as adoptive T-cell transfer, interleukin-2, and cancer vaccines.

Emerging reports have also suggested that lymphopenia may be associated with intensive care unit admission and ARDS in patients with COVID-19. This finding, in correlation with the lack of efficacy of steroid treatment for previous coronavirus-related pandemics, suggests that steroids should be avoided in the treatment of COVID-19 until further evidence for their use surfaces. 

Furthermore, given the accumulating evidence of cytokine storm leading to multi-organ failure and death associated with COVID-19, researchers recommended that immune-based treatments that are known to cause cytokine release syndrome should be deferred. If deemed necessary however, patients should undergo asymptomatic screening for COVID-19 prior to initiation, also keeping in view that the sensitivity of a polymerase chain reaction–based test is not known.

“While longitudinal serological studies are awaited, emerging evidence suggests that primary SARS-CoV-2 may render natural immunity and could protect a survivor from subsequent infections,” the authors wrote. “Although this is critical information for vaccine development, loss of lives with prior coronavirus outbreaks (severe acute respiratory syndrome–associated coronavirus and Middle East respiratory syndrome coronavirus) taught us that damage prevention is imperative and astronomically more effective than damage control, particularly for elderly patients and those with underlying conditions.”

Reference:

Abid MB, Mughal M, Abid MA. Coronavirus Disease 2019 (COVID-19) and Immune-Engaging Cancer Treatment. JAMA Oncology. doi:10.1001/jamaoncol.2020.2367.