Concern Over Response to COVID-19 in Patients With Blood Cancers

Liam Davenport

January 12, 2021

Editor's note: Find the latest COVID-19 news and guidance in Medscape's Coronavirus Resource Center.

Patients with cancer, particularly those with solid tumors, mounted an immune response to COVID-19 similar to that seen in people without cancer, but among patients with hematologic cancers, immune responses were less pronounced and were highly variable, typically taking longer to clear the virus.

The findings come from a small UK study published online January 4 in Cancer Cell as a fast-track preprint article.

The findings may have implications for vaccinating against COVID-19, say the researchers, led by Sheeba Irshad, MD, PhD, a Cancer Research UK clinician scientist based at King's College London, London, United Kingdom.

"Our study provides some confidence and reassurance to care providers that many of our patients with solid cancers will mount a good immune response against the virus, develop antibodies that last, and hopefully resume their cancer treatment as soon as possible," Irshad said in a statement.

"These conclusions imply that many patients, despite being on immunosuppressive therapies, will respond satisfactorily to COVID-19 vaccines," she added.

Although "the data would suggest that solid cancer patients are likely to mount an efficient immune response to the vaccine...the same cannot be said for hematological cancers, especially those with B-cell malignancies," Irshad told Medscape Medical News.

"They may be susceptible to persistent infection despite developing antibodies, so the next stage of our study will focus on monitoring their response to the vaccines.

"At present, the best way to protect them alongside vaccinating them may be to vaccinate all their healthcare providers and carers to achieve herd immunity and continue to respect the public health measures put in place," such as wearing a mask, praticing social distancing, and testing asymptomatic persons, she commented.

Study Details

This study, known as the SARS-CoV-2 for Cancer Patients (SOAP) study, involved 76 patients with cancer; 41 of these patients had COVID-19, and 35 served as non-COVID cancer control patients.

Peripheral blood was collected from all patients; multiple samples were taken every 2 to 4 days where possible.

The COVID-19 and control groups were matched for age, body mass index, and tumor type, and both groups included patients with solid and hematologic cancers.

The groups were also comparable in terms of the proportion of patients with stage IV disease, those who received palliative as opposed to radical treatment, and patients who were treated within 4 weeks of recruitment to the study.

The results showed that 24.4% of cancer patients who were exposed to COVID-19 remained asymptomatic; 21.9% had mild disease; 31.7%, moderate disease; and 21.9%, severe disease.

Patients with hematologic cancers were more likely to experience dyspnea than those with solid tumors, and 39% received corticosteroid/antiviral therapies that specifically targeted COVID-19 infection.

The median duration of virus shedding was 39 days across the whole cohort. It was notably longer among patients with hematologic cancers, at a median of 55 days, vs 29 days for patients with solid tumors.

Of 46 patients who survived beyond 30 days and for whom complete data were available, the team found that those with moderate or severe COVID-19 were more likely to be diagnosed with progressive cancer at their next assessment in comparison with those who were asymptomatic with COVID-19 or with control patients.

Solid-cancer patients with moderate/severe COVID-19 had sustained lymphopenia and increased neutrophil-to-lymphocyte ratios up to days 40 to 49 of the infection, whereas among those with mild infection, clinical blood parameters were typically in the normal range.

Although overall blood profiles of patients with hematologic cancers were similar to those of patients with solid cancers, the trajectories between mild and moderate/severe COVID-19 overlapped, and there was a large degree of heterogeneity between patients.

The team also reports that among patients with solid tumors, all parameters returned to values that were close to baseline 4 to 6 weeks after the patients tested negative for COVID-19 on nasopharyngeal swabbing; by contrast, many of the patients with hematologic cancers experienced ongoing immune dysregulation.

Further analysis revealed differences in immune signatures between patients with solid cancers who had active SARS-CoV-2 infection and noninfected control patients. The former showed, for example, IL-8, IL-6 and IL-10, IP-10 enrichment.

In contrast, there were few differences between infected and noninfected hematologic cancer patients.

Across both cohorts, approximately 75% of patients had detectable antibodies against COVID-19. Antibodies were sustained for up to 78 days after exposure to the virus.

However, patients with solid tumors showed earlier seroconversion than those with hematologic cancers. The latter had more varied responses to infection, displaying three distinct phenotypes:

  • Failure to mount an antibody response, with prolonged viral shedding, even beyond day 50 after the first positive swab;

  • An antibody response but failure to clear the virus;

  • An antibody response and successful clearing of the virus.

The team notes that overall, patients with hematologic cancers showed a mild response to COVID-19 in the active/early phases of the disease and that the response grew stronger over time, similar to the immune changes typically seen with chronic infections.

This was particularly the case for patients with cancers that affect B cells.

The team acknowledges that there are several limitations to the study, including its small sample size and lack of statistical power to detect differences between, for example, different treatment modalities.

"An important question which remains unanswered is if a 'reinforced' immune system following immunotherapy results in an under-/over-activation of the immune response" to COVID-19, the investigators comment. They note that one such patient had a good response.

The SOAP study is sponsored by King's College London and Guy's and St Thomas' Foundation NHS Trust. It is funded from grants from the KCL Charity funds, MRC, Cancer Research UK, program grants from Breast Cancer Now at King's College London and by grants tothe Breast Cancer Now Toby Robin's Research Center at the Institute of Cancer Research, London, and the Wellcome Trust Investigator Award, and is supported by the Cancer Research UK Cancer Immunotherapy Accelerator and the UK COVID-Immunology-Consortium. The authors have disclosed no relevant financial relationships.

Cancer Cell. Published online January 4, 2021. Abstract

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