Convalescent plasma shows survival benefit for patients with blood cancer, COVID-19
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Convalescent plasma treatment appeared associated with a reduction in 30-day mortality among patients with hematologic malignancies hospitalized for COVID-19, according to study results published in JAMA Oncology.
“In patients with blood cancers who are hospitalized due to COVID-19, it would appear that convalescent plasma may be of benefit,” Jeremy L. Warner, MD, MS, FAMIA, FASCO, associate professor of medicine and biomedical informatics in the division of hematology/oncology at Vanderbilt University, told Healio. “This is a group of patients who usually have severe underlying immunodeficiencies, due to the cancer itself and/or the treatment. Thus, one would expect that they cannot make their own antibodies in response to the virus.”
Warner and colleagues compared 30-day all-cause mortality data from the COVID-19 and Cancer Consortium registry between March 17, 2020, and Jan. 21, 2021, among 143 convalescent plasma recipients (31.5% aged 60-69 years; 57.3% men; 56.6% white) and 823 untreated controls (28.3% aged 60-69 years; 55.5% men; 50.2% white). All patients had hematologic cancers and COVID-19 and were hospitalized across multiple institutions.
“The first reason for conducting this study was that by the fall of 2020, we had built the [COVID-19 and Cancer Consortium] database to the point where we could start asking targeted questions about subgroups. Prior to that, we were only able to take broad strokes across the entire population,” Warner said. “The second reason is serendipity — a conversation started on Twitter with one of the national convalescent plasma experts, Michael Joyner, MD, at Mayo Clinic. This conversation led directly to this project.”
Median follow-up was 30 days (interquartile range, 21-90), at which time the overall 30-day mortality rate was 23.1%.
Treatment with convalescent plasma was associated with a reduction in 30-day mortality (HR = 0.6; 95% CI, 0.37-0.97), which remained significant after propensity score matching (HR = 0.52; 95% CI, 0.29-0.92).
Moreover, the propensity-score matched comparison also showed a reduction in risk for 30-day mortality with convalescent plasma among the 338 patients admitted to the ICU (HR = 0.4; 95% CI, 0.2-0.8) and among the 227 patients who required mechanical ventilation (HR = 0.32; 95% CI, 0.14-0.72).
Of note, more patients in the convalescent plasma group experienced bleeding (11.2% vs. 4.2%), sepsis (40.6% vs. 22.4%), respiratory failure (69.2% vs. 46.2%) and congestive heart failure (7% vs. < 3.5%).
“Our study is the first to show, to our knowledge, a COVID-19 treatment with a statistically significant survival benefit in patients with cancer,” Warner said.
“There are two important points,” he added. “First, patients with cancer were nearly systematically excluded from many of the prospective treatment trials or the cancer status was not recorded. Second, these findings must not be considered definitive, due to the retrospective nature of the study. In a perfect world, a well-designed prospective clinical trial would be carried out to confirm the findings.”
Further research will look into the associations of treatment for COVID-19 — including convalescent plasma but also other treatments, such as remdesivir (Veklury, Gilead) and monoclonal antibodies — with outcomes among patients with cancer, Warner added.
“We will also hope to learn about the interplay of vaccines, COVID-19 severity and whether vaccinated patients who do not respond to the vaccine or who ‘seroconvert’ might benefit from convalescent plasma and/or monoclonal antibodies,” he said.
Although real-world data like those used in this analysis have the potential to quickly provide actionable information, the study may be limited by its time-to-event analysis design, according to an accompanying editorial by Gregory S. Calip, PharmD, MPH, PhD, Rebecca A. Miksad, MD, MPH, and Somnath Sarkar, PhD, all researchers at Flatiron Health Inc.
For instance, the study may be limited by survival bias, because only surviving patients had the opportunity to undergo plasma treatment, as well as immortal time bias, because exposure to convalescent plasma may have occurred at any point during hospitalization.
“This study ... is an important starting point to guide emerging clinical evidence on the use of convalescent blood products in patients with hematologic malignancies with severe COVID-19 illness,” the editorial authors wrote. “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. Determining a causal treatment effect of convalescent plasma will ultimately require an appropriately designed clinical trial.”
For more information:
Jeremy L. Warner, MD, MS, FAMIA, FASCO, can be reached at Vanderbilt University, 2220 Pierce Ave., 777 PRB, Nashville, TN 37232; email: jeremy.warner@vumc.org.
References:
Calip GS, et al. JAMA Oncol. 2021;doi:10.1001/jamaoncol.2021.1715.
Thompson MA, et al. JAMA Oncol. 2021;doi:10.1001/jamaoncol.2021.1799.
Perspective
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Henry Chi Hang Fung, MD, MBChB, FACP, FRCPE
In U.S. and Europe, the COVID-19 pandemic appears to be under better control largely due to unprecedented efficacy of the vaccines. Current data suggest that the efficacy of vaccination appeared suboptimal among patients with underlying hematologic malignancies and for those who were immunocompromised. The outcomes of COVID-19 infection for patients with hematologic malignancies also were less favorable. Taken together, better treatments for COVID-19 remain a high priority, specifically but not limited, to our patients with blood cancers.
In this study, convalescent plasma treatment was associated with a significantly improved 30-day mortality in the 143 individuals who received it. This association remained significant after propensity score matching. A randomized study will be required to confirm the efficacy, although the results from this large cohort study look promising.
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