Insights from decades of cancer research are surprisingly transferable to the battle against COVID-19. The desire to save life and ease suffering that motivates cancer researchers has been directed to the new disease as well.
Drawing on their knowledge of cancer drug mechanisms, and of the adverse side effects of some of those drugs, Dana-Farber scientists are helping lead an array of clinical trials of potential treatments for COVID-19.
Their work has special urgency given the dearth of approved drugs to prevent or treat COVID-19. (Just one drug, remdesivir, has been approved by the U.S. Food and Drug Administration to treat the disease.) The alacrity with which Institute researchers and others have taken up the challenge of COVID-19 has allowed trials to be launched with unusual speed.
Here is a look at some of their work.
Testing the drug ibrutinib
Steven Treon, MD, PhD, director of the Bing Center for Waldenström’s Macroglobulinemia, is principal investigator (PI) of a trial of the drug ibrutinib in patients with COVID-19. The trial follows several case reports in which ibrutinib appeared to protect against lung damage and respiratory distress caused by the coronavirus. The drug targets molecular pathways that are overactive in both Waldenström’s, where it affects the bone marrow, and the lungs of patients with COVID-19.
Remdesivir safety and effectiveness
Francisco Marty, MD, an infectious disease physician at Dana-Farber and Brigham and Women’s Hospital, is principal investigator of two clinical trials of remdesivir, one involving patients with moderate COVID-19 and one in patients with severe cases of the disease. The drug works by “tricking” the virus into incorporating a component of the drug into the virus’s RNA, halting viral replication. The phase 3 trial will compare the safety and effectiveness of remdesivir to the current standard care for COVID-19.
Antibody-rich convalescent plasma
In the ESCAPE trial, patients hospitalized with moderate cases of COVID-19 are being treated with plasma from people who have recovered from the disease.
Convalescent plasma — the antibody-rich liquid portion of blood from survivors of viral illnesses — has been used for decades to treat patients with those illnesses, but the approach has never been tested in a carefully controlled, randomized clinical trial. The ESCAPE trial is among the first to do so.
The principal investigator of the study is Richard Kaufman, MD, medical director of the transfusion service at Brigham and Women’s Hospital, and the chief protocol architect is Clifton Mo, MD, director of autologous stem cell transplantation for multiple myeloma at Dana-Farber.
Testing the drug defibrotide
Paul Richardson, MD, clinical program leader and director of clinical research at the Jerome Lipper Multiple Myeloma Center at Dana-Farber, has worked with colleagues in Europe to launch trials of the drug defibrotide in Spain, Italy, the United Kingdom, and Ireland for patients with COVID-19, with preliminary results in Spain showing promise.
Used to treat hepatic veno-occlusive disease (VOD), a dangerous potential side effect of stem cell transplants, defibrotide protects the inner lining of blood vessels — called the endothelium — from specific inflammation-related forms of damage. Recent studies have shown that infection by the novel coronavirus can produce similar kinds of endothelial cell injury.
Richardson was an initiator and driving force behind trials of defibrotide in patients undergoing stem cell transplant complicated by VOD as well as other forms of endotheliitis (inflammation of the endothelium) and is helping lead the effort to study its potential benefits in COVID-19. He is also directing a study at Dana-Farber/Brigham and Women’s Cancer Center with Robert Soiffer, MD, and Clifton Mo, MD, of Dana-Farber, and Rebecca Baron, MD, Anthony Massaro, MD, Gerald Weinhouse, MD, of Brigham and Women’s Hospital, and others.
Evaluating immunological responses to the novel coronavirus
Irene Ghobrial, MD, director of the Center for Prevention of Progression of Blood Cancers, and her laboratory are providing comprehensive and correlative science across these studies. They’re also evaluating the immunological responses to the novel coronavirus to better understand the immunological mechanisms that underlie the disease and its consequences. This is particularly important given that numerous studies have shown that patients with lymphoid and plasma cell malignancies are at particular risk of complications from COVID-19.
A survey led by Ken Anderson, MD, program director at the Jerome Lipper Multiple Myeloma Center and LeBow Institute for Myeloma Therapeutics, and Nikhil Munshi, MD, director of Basic and Correlative Science at the Lipper Center, in their leadership roles in the International Myeloma Society, has added substantially to this evidence base.
Understanding short- and long-term impact of COVID-19
Ghobrial and her colleagues are launching a study to identify the prevalence and development of COVID-19 in patients with precursor conditions to hematologic cancers and in healthy populations. Called IMPACT, it is enrolling about 5,000 people nationwide who will have a blood test for antibodies indicating exposure to the novel coronavirus and will have additional blood samples collected for testing over a one-year period. The goal is to understand the short- and long-term impact of COVID-19 on the immune system of healthy individuals and those with underlying immune problems, who may be at high risk of poor outcomes.
Janus kinase inhibitors
In the PRE-VENT trial (currently in phase 3), researchers are trying to determine if the drug pacritinib can prevent acute respiratory distress syndrome and ventilation for hospitalized patients with severe COVID-19.
Pacritinib is a Janus kinase inhibitor (or JAK inhibitor) currently being developed for the treatment of myeloproliferative neoplasms, specifically myelofibrosis — a rare form of cancer in which bone marrow is replaced by scar tissue.
Janus kinase inhibitors are potent immune modifying drugs that interfere with a cell process known as JAK-STAT signaling. One function of that process is to produce cytokines — small proteins that activate the body’s immune and inflammation responses. By binding to specific proteins in the signaling process, JAK inhibitors can help reduce excesses of the body’s immune system.
Both malignant blood cancer cells and infection with the coronavirus release excess amounts of cytokines. Researchers including David Steensma, MD, clinical director of the Center for Prevention of Progression at Dana-Farber, and Richard Stone, MD, chief of staff at Dana-Farber and director of Translational Research in the Adult Leukemia Program, along with their colleagues at Brigham & Women’s Hospital, are trying to determine if pacritinib can prevent patients from experiencing a “cytokine storm,” which leads to excess inflammation in the lungs and the patient’s immune system attacking its own cells and tissues.