Antibody therapy with Covid-19 convalescent plasma may confer survival benefits to immunocompromised patients with hematologic cancers who have been hospitalized with Covid-19; however, rates of sepsis, respiratory complications, bleeding, and congestive heart failure were also significantly higher, according to results from a recent study published in JAMA Oncology.
“Patients with hematologic cancers represent a distinctive subset of patients with Covid-19 caused by immune deficits associated with both the diseases themselves and their treatments. Hematologic cancers have been consistently associated with increased Covid-19 mortality and other complications,” wrote Jeremy L. Warner, MD, MS, of Vanderbilt University, Nashville, Tennessee, and fellow researchers from the Covid-19 and Cancer Consortium. “Hematologic cancers are associated with defects in humoral and cellular immunity that may contribute to adverse Covid-19 outcomes.”
Previous studies found that antibody therapy with Covid-19 convalescent plasma offered benefits in the general population and for elderly patients, particularly when high titer units were given early on, they added.
To assess whether convalescent plasma therapy corrects the defects in humoral deficiency that often result in patients with hematologic cancers, and improves outcomes, Warner and colleagues conducted this retrospective study. Using data from the Covid-19 and Cancer Consortium registry, they identified 996 patients (mean age: 65 years; 55.8% male) with hematologic cancers hospitalized for Covid-19 who had undergone convalescent plasma treatment at any time during their hospitalization.
The main outcome was 30-day all-cause mortality, and a secondary subgroup analyses on patients with severe Covid-19 who required mechanical ventilatory support and/or ICU admission was also performed.
In all, 143 patients received convalescent plasma, and 823 untreated patients served as controls. After a median follow-up of 30 days, 223 deaths (23.1%) occurred within 30 days of a diagnosis of Covid-19. Treatment with convalescent plasma was associated with improved 30-day mortality (HR: 0.60; 95% CI: 0.37-0.97), and this association was still significant after propensity score matching (HR: 0.52; 95% CI: 0.29-0.92).
The crude mortality rate was significantly lower in convalescent plasma recipients compared with nonrecipients (13.3% versus 24.8%, respectively), and the difference was statistically significant after adjustment in the overall comparison (HR: 0.60; 95% CI: 0.37-0.97; P=0.03) and in the propensity score–matched comparison (HR: 0.52; 95% CI: 0.29-0.92; P=0.03).
In all, 338 patients were admitted to the ICU, and among those who received convalescent plasma, mortality was significantly lower compared with those who did not (HR for propensity score-matched comparison: 0.40; 95% CI: 0.20-0.80). Mortality was also significantly lower in patients who received convalescent plasma among the 227 patients requiring mechanical ventilatory support (HR for propensity score-matched comparison: 0.32; 95% CI: 0.14-0.72).
Convalescent plasma recipients, however, had a higher incidence of bleeding compared with control patients (11.2% versus 4.2%, respectively), sepsis complications (40.6% versus 22.4%), respiratory failure (69.2% versus 46.2%), and congestive heart failure (7% versus <3.5%).
“Notably, despite superior survival in the convalescent plasma group, there were considerably more sepsis and respiratory complications in this group. This finding likely reflects a higher severity of SARS-CoV-2 infection rather than complications from the treatment, although this possibility cannot be entirely excluded. Adverse effects of protein-rich infusions can include thromboses, kidney injury, and volume overload. It is reassuring that the rates of thromboses are low in both recipients and nonrecipients and the rates of acute kidney injury are similar,” Warner and colleagues wrote. The incidence of hepatic and kidney injuries was similar in both groups, with acute hepatic injury occurring in 5.6% of patients treated with convalescent plasma, compared with 4.9% of control patients, and acute kidney injury in 25.9% versus 27.5%, respectively. Researchers also recorded low rates of the following in convalescent plasma recipients compared with controls:
- Venous thrombosis: 10.5% versus 8.4%, respectively.
- Arterial thrombotic events: 3.5% versus <3.5%.
- Arrhythmias: 3.5% versus <3.5%.
“This study by Thompson et al is an important starting point to guide emerging clinical evidence on the use of convalescent blood products in patients with hematologic cancer with severe Covid-19 illness. Despite the potential limitations from time-related biases described here and other residual confounding from unmeasured factors in this nonrandomized study, the consistent directionality and significance of the effect estimates reported is encouraging,” wrote Gregory S. Calip, PharmD, MPH, PhD, of Flatiron Health Inc., New York, and the University of Illinois at Chicago, College of Pharmacy, in an invited commentary.
In addition, its retrospective nature and unmeasured variables, other study limitations include a possible bias due to time to treatment and time from Covid-19 diagnosis, lack of data on timing and sequence of other treatments, differences in hematologic cancer types and stages among patients, differences in care, and short duration.
Study results suggest that the administration of convalescent plasma to patients with hematologic cancers who are hospitalized for Covid-19 confers a potential survival benefit.
Convalescent plasma treatment was associated with a significantly improved 30-day mortality.
Liz Meszaros, Deputy Managing Editor, BreakingMED™
This project has been funded in whole or in part with federal funds from the US Department of Health and Human Services, Office of the Assistant Secretary for Preparedness and Response, Biomedical Advanced Research and Development; and grants from the National Cancer Institute, the National Center for Advancing Translational Sciences, the Schwab Charitable Fund, the United Health Group, the National Basketball Association, Millennium Pharmaceuticals, Octapharma USA Inc., the American Cancer Society and Hope Foundation for Cancer Research, the Longer Life Foundation: A RGA/Washington University Partnership, and the Mayo Clinic.
Warner reported no disclosures.
Calip reported receiving grants from Pfizer outside the submitted work, and current employment with Flatiron Health, Inc, which is an independent subsidiary of the Roche group, and stock ownership in Roche.
Cat ID: 118
Topic ID: 78,118,500,501,521,728,932,730,933,118,190,926,192,927,151,928,925,934