“Much of the organ damage in COVID-19 does not result from the viral infection itself but rather from the immune system’s maladaptive overreaction after the initial illness,” said Mark Sloan, MD, Associate Professor of Medicine, Boston University School of Medicine. “A current crop of trials focuses on how to safely and effectively attenuate the immune system during viral infection. Several key cytokines, such as IL [interleukin]-6 and IL-1, are elevated in these patients and have been observed to correlate with the severity of illness.”
This overactive immune response resembles hemophagocytic lymphohistiocytosis (HLH), which Dr Sloan noted has established treatment approaches.
“The most accepted strategy is the use of combination etoposide and dexamethasone,” he said. “It has been a straightforward step to open up a trial of this strategy for severe COVID infections using a modified HLH study protocol. This is something we could uniquely do as oncologists, because of prescribing restrictions and the side-effect profile with etoposide,” Dr Sloan added.
Other anticancer agents with potential promise in COVID-19 include Janus kinase inhibitors, such as ruxolitinib (Jakafi) and tofacitinib (Xeljanz). “Robust preclinical and clinical data suggest their activity in hyperinflammatory syndromes,” said Kevin O’Hayer, MD, PhD, Senior Director, Immuno-oncology, Incyte Corporation. He described positive early findings for ruxolitinib in 2 small studies, including one study with 43 patients in Wuhan, China, and another study at Yale School of Medicine.
Because activated macrophages have toll-like receptors, Bruton tyrosine kinase inhibitors, such as ibrutinib (Imbruvica), are also being studied in the treatment of COVID-19, said David DeRemer, PharmD, BCOP, FCCP, FHOPA, Clinical Associate Professor, Department of Pharmacotherapy and Translational Research, University of Florida College of Pharmacy. “Some retrospective data from Europe suggest that patients treated with ibrutinib did have better outcomes, although the paper did have some limitations,” Dr DeRemer noted.
Dr DeRemer also described a small prospective US study of the off-label use of acalabrutinib (Calquence) in 19 patients with COVID-19, which reduced respiratory distress and the overactive immune response in most of the patients who received the drug.
Michael Joyner, MD, an anesthesiologist at the Mayo Clinic, is leading the national program sponsored by the US government to coordinate the collection and distribution of convalescent plasma for the treatment of individuals with severe or life-threatening COVID-19 infection.
“As of this morning, we had 58,000 patients enrolled in the protocol at nearly 2000 sites ranging from small institutions in Casper, Wyoming, and Lawton, Oklahoma, to major academic medical centers,” he said.
“We have found that the material is safe,” Dr Joyner said. “So far, our data suggest that if convalescent plasma is given to patients early on, when they are just admitted to the hospital, that has the best chance of success,” Dr Joyner said.
Dr Markman asked Dr Joyner about the use of another common anticancer drug, dexamethasone, in the treatment of COVID-19.
“I’ve looked in detail at the recovery trials,” Dr Joyner responded. “When doses were restricted primarily to patients on mechanical ventilation with acute respiratory distress syndrome, the mortality dropped from around 40% to the mid to high 20% range. On the other hand, mortality increased a little in people who were less severe, so it is a double-edged sword. This should be an ICU [intensive care unit]-based therapy in people starting to develop full-blown hyperinflammatory response. I would argue that early treatment with convalescent plasma makes sense, and then if you get into a fire drill in the ICU, dexamethasone makes sense,” he concluded.