Discussion
plasmaAntivirals, cancer, cancer an increase
VIRUS, CANCER, HEMATOLOGICAL MALIGNANCIES, RECRUITMENT, SECONDARY, PEARLY DISEASE
The results of this trial provide evidence that patients with cancer (group 1) who develop severe COVID-19 benefit from anti-SARS-CoV-2 plasma from convalescent/vaccinated donors and experience improved overall recovery. Although the size of group 1 was relatively small, with 56 patients, differences in the primary endpoint were substantial (13 versus 31 d) and are supported by earlier discharge and improved overall survival. The likelihood of improved outcomes upon plasma therapy was substantial for patients with cancer, with shortened time to the primary endpoint, time to discharge and also survival. In contrast, no benefits were observed in groups 2–4, pointing toward a specific benefit of vaccinated/convalescent plasma in patients with cancer.These results from a specifically designed clinical trial are in line with two retrospective propensity-matched cohort analyses with a total of 244 patients treated with plasmaAntivirals and monoclonal antibodies for COVID-19 are most effective in early disease stages and are usually not recommended beyond 5 d after symptom onset. The same was shown for early convalescent plasma therapy in a prehospital setting without the need for supplemental oxygenUnlike monoclonal antibodiesOur study has limitations. Compared with studies with nonselected patients, the overall cohort was relatively small. Also, while the overall cohort was well balanced, we observed imbalances between enrollment arms (for example, with respect to age, sex, comorbidities and therapy) in the subgroups. Therefore, we adjusted for the two variables (that is, age and sex) most likely to be associated with outcomes in a sensitivity analysis, which did not impact on the primary outcome in group 1. Another limitation could be the open-label design of our trial. However, the primary endpoint results for subgroups are supported by the secondary endpoint results for overall survival and neutralizing activity, showing the unique effectivity of plasma therapy in patients with cancer.The group of patients with cancer was diverse, with most patients suffering from hematological malignancies. Thus, the conclusions might not be applicable to all types of cancer. Lastly, recruitment occurred over an extended time span with different virus variants and evolving standards of care. Nonetheless, randomization was in place and plasma was obtained during the respective waves of the pandemic. Our conclusions cannot formally be extended to novel variants not covered within the trial (starting with Omicron). While studies have suggested that neutralizing antibodies were broadly active before Omicron, the Omicron variant in particular has shown that variant-specific plasma would be important to control virus replicationThere are several strengths of our trial. Plasma was obtained from donors with confirmed high titers of neutralizing antibodies, as indicated by the fact that <20% of patients in the donor pool met the criteria (≥1:80 titer and corresponding high saturation in the NeutraLISA; Extended Data Fig. We found that in patients with cancer an increase in neutralizing antibodies was observed after plasma infusion, which further supports the restriction of the beneficial effects of plasma to patients with limited ability to react to the antigen with a humoral response. While the subgroup analysis was exploratory, the effect sizes were substantial. Given the limited available effective treatment options for patients with cancer and the favorable safety profile, convalescent/vaccinated plasma should be considered. Further confirmation of the findings is expected to come from other larger trials (for example, REMAP-CAP).Taken together, these data suggest that plasma therapy may improve outcomes in patients with cancer with severe COVID-19.