Fred Hutch physician Dr. Eduardo Sanchez enjoys asking clinical questions that can ultimately “help us become better physicians, such as finding strategies which we can implement and rapidly improve our day-to-day care for our patients.” As an infectious disease specialist, Dr. Sanchez focuses on immune compromised patients. For these individuals—including those with hematologic malignancies or who have undergone hematopoietic cell transplantation (HCT)—there is an increased risk of poor outcomes due to infection. This is especially true for infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Because of this heightened risk, when an immunocompromised patient tests positive for SARS-CoV-2, a major concern of Fred Hutch physicians has been “to get treatment to these patients as soon as possible,” describes Dr. Sanchez.
One effective therapy that can reduce the risk of severe COVID-19 complications is administration of neutralizing antibodies directed against the SARS-CoV-2 spike protein. These neutralizing antibodies bind to the spike protein and prevent the virus from being able to enter our cells. One such agent is bebtelovimab, a neutralizing monoclonal antibody that received emergency use authorization from the Federal Drug Administration (FDA) in February 2022 to treat mild-to-moderate COVID-19. However, there is limited data on this drug’s effectiveness for the treatment of COVID-19, or in preventing persistent infection, among cancer patients. This is especially critical for immunosuppressed individuals with hematologic malignancies who have a greater risk of developing persistent infection. While this authorization was rescinded in November 2022 (as bebtelovimab lost potency against newer SARS-CoV-2 variants), its use provided an opportunity to demonstrate the effectiveness of neutralizing monoclonal antibodies such as this on cancer patients or immunosuppressed individuals.
To assess the clinical outcomes of cancer patients treated with this therapy, Dr. Sanchez thought a retrospective study on patients that had received bebtelovimab would help us understand whether this drug was effective in this patient population and inform treatment approaches for novel monoclonal antibodies as they are approved for use. To ask if this drug was effective at preventing adverse outcomes related to COVID-19 infection in immunosuppressed patients, Dr. Sanchez led a retrospective cohort study of adult patients with COVID-19 infection who received bebtelovimab at Fred Hutchinson Cancer Center between March and November 2022. Most of these patients had an underlying hematologic malignancy, with almost a quarter of patients having received hematopoietic cell transplantation. While spearheading this study, recently published in Transplant Infectious Disease, Dr. Sanchez worked alongside other Fred Hutch researchers and under the mentorship of Drs. Catherine Liu and Steven Pergam— both physicians and Professors at Fred Hutch who are part of the Vaccine and Infectious Disease Division.
Dr. Sanchez says that he was “pleasantly surprised by the overall good outcomes of the patients in the study.” Despite this population having a high risk of developing COVID-related complications, most patients who received bebtelovimab recovered well from COVID-19 at home without requiring hospitalization, and only a few patients experienced some persistent infection. For those patients with persistent infection, Dr. Sanchez adds that this is something they’re actively studying— what makes some patients experience long-lasting effects of COVID-19 and how they can improve treatment for these individuals. While this work found that bebtelovimab was largely effective at treating COVID-19 in immune-compromised patients, perhaps the most impressive aspect of this work was the coordinated care approach implemented to provide rapid care for the patients—often getting this drug to patients within two days of testing positive for SARS-Cov-2 infection. Dr. Sanchez remarks on how it took a lot of logistics to develop the infrastructure required to get these patients drugs quickly, and that this fact “goes hand in hand with the good outcomes we were seeing.” The execution of this rapid COVID-19 response treatment plan required close coordination across various Fred Hutch medical teams and departments, but ultimately it enabled Fred Hutch to provide care to at-risk patients as soon as possible to improve outcomes of SARS-CoV-2 infection.
Dr. Sanchez emphasizes his gratitude for his research mentors, Drs. Liu and Pergam, who have enabled him to conduct this research. He also stresses that the rapid COVID-19 treatment plan that they were able to implement was not a one-person operation; it required multidisciplinary coordination of many different individuals including nurses, pharmacists, the infection prevention team and attending physicians. While it took a bit of time to work out, Dr. Sanchez explains that this was truly a team effort that enabled rapid care to Fred Hutch patients, and he is proud to have been a part of this team.
This work was supported by the National Institutes of Health.
Fred Hutch/UW/Seattle Children’s Cancer Consortium members Drs. Catherine Liu and Steven Pergam contributed to this work.
Sanchez E, Krantz EM, Yoke L, Gallaher M, Bhattacharyya P, So L, Escobar ZK, Tverdek F, Rosen EA, Quinn ZZ, Swetky M, Walji S, Wilson MH, McCreery B, McCulloch D, Weixler A, Roychoudhury P, Pergam SA, Liu C. Clinical outcomes and frequency of persistent infection among immunosuppressed patients treated with bebtelovimab for COVID-19 infection at an ambulatory cancer center. Transpl Infect Dis. 2024.