Anti-CD20 therapy increases complication risk in COVID-19 for blood cancer patients

16th January 2023

Anti-CD20 therapy for haematological cancer patients is linked to an increased risk of adverse outcomes despite triple vaccination

Anti-CD20 therapy use in patients with haematological cancers, despite triple vaccination, still poses an increased risk for adverse outcomes following a breakthrough COVID-19 infection, according to the findings of a retrospective population-based cohort study by Canadian researchers.

Although patients with cancer were excluded from the initial clinical trials of COVID-19 vaccines, emerging evidence suggested that adult patients with haematological malignancies, infected with the virus, especially those who were hospitalised and over 60 years of age, were at an increased risk of death. Moreover, once vaccinated, it became clear that patients with haematological cancers displayed an impaired humoral response and the recognition that breakthrough infections were possible and that these infections were correlated with the level of neutralising antibody titers during the peri-infection period, researchers hypothesised that haematological malignancy patients and even those with other types of cancer, might experience a more severe outcomes if infected with COVID-19.

In the present study, the Canadian team set out to examine the relative risk of COVID-19 breakthrough infections and COVID-19-related outcomes in vaccinated patients with cancer (including haematological and solid tumours) compared to matched non-cancer controls. In addition, they considered whether current treatment of cancer, with for example, anti-CD20 therapy, impacted on the risk of COVID-related outcomes. Using a retrospective design, researchers matched patients with haematologic cancer to non-cancer controls (1:4), based on age, sex, type of vaccine, date of vaccine. The primary outcome was COVID-19 breakthrough infection, whereas secondary outcomes were emergency department visits, hospitalisation and death within 4 weeks of infection and the outcomes adjusted for gender, age socioeconomic status and vital status.

Anti-CD20 therapy and COVID-19 outcomes

A total of 289,400 vaccinated cancer patients with a mean age of 66.05 years (65.4% female) were matched with 1,157,600 non-cancer controls. During the period of the study, there were 3118 and 12 150 breakthrough infections in the cancer and non-cancer groups, respectively.

Overall, the risk of a COVID-19 breakthrough infection was significantly higher among cancer patients compared to non-cancer controls (adjusted Hazard ratio, aHR = 1.05, 95% CI, 1.01 – 1.09, p = 0.02). However, the risk was significantly greater among patients with haematologic cancers (aHR = 1.33, 95% CI 1.20 – 1.46, p < 0.01) compared to controls. There were also significantly elevated risks for haematological cancer patients (compared to controls) for emergency department visits, hospitalisation and death. However, when researchers looked at patients who had received a third COVID-19 vaccine dose, this was associated with lower risk of breakthrough infection for blood cancer patients (aHR = 0.61, 95% CI 0.54. – 0.69, p < 0.01). 

Among haematological cancer patients in receipt of anti-CD20 therapy, there remained an elevated risk of breakthrough infection (aHR = 1.88, 95% CI 1.27 – 2.78, p =0.02) as well as for emergency department visits, hospitalisation and death. Although a third vaccine dose was associated with a lower risk of infection and COVID-19 complications for all cancer patients, this did not significantly reduce the risk among haematological cancer patients receiving anti-CD20 therapy. For example, the adjusted hazard ratio for death was 0.49 (p = 0.24) and 1.19 (p = 0.46) for severe outcomes.

The authors concluded that patients with haematological cancer had the highest risk for breakthrough infections and adverse COVID-19 outcomes, particularly for those who received anti-CD20 therapy.

Citation
Gong IY et al. Association of COVID-19 Vaccination With Breakthrough Infections and Complications in Patients With Cancer. JAMA Oncol 2022.

Improved clinical outcomes for haematological malignancy COVID-19 patients after convalescent plasma therapy

13th April 2022

Haematological malignancy patients infected with COVID-19 appear to achieve improved clinical outcomes after receiving convalescent plasma therapy

Haematological malignancy patients infected with COVID-19 can expect better clinical outcomes after receipt of convalescent plasma according to the results of a pre-print systematic review by researchers from the Department of Biomedical Science, Qatar University, Doha, Qatar.

Patients with any form of cancer have been deemed particularly vulnerable to infection with COVID‐19 given how immunodeficiency is a secondary consequence of their cancer treatment. Convalescent plasma (CP) therapy is a type of passive immunity whereby plasma enriched with specific antibodies generated by patients who have recovered from a specific infection, is transfused into other patients.

The possible value of CP in those with cancers such as a haematological malignancy, the the authors of one study conclude that convalescent plasma may be a promising therapy in cancer patients with COVID-19. Despite these potentially promising results, the use of convalescent plasma therapy among patients with cancer, especially those with a haematological malignancy has not been systematically reviewed.

For the present study, the Qatarian team focused on haematological malignancies and searched for studies that included patients infected with COVID-19, based on a PCR confirmed result and who were treated with convalescent plasma. Included studies were those reported in English and either randomised trials or prospective and retrospective comparative cohort studies.

The authors extracted malignancy data and set several primary outcome measure of clinical improvement including mortality, viral clearance and recovery one month post-treatment. The main secondary outcome was adverse events after use of convalescent therapy.

Haematological malignancy outcomes and convalescent plasma

A total of 17 studies with 1103 patients of whom 258 had one or more haematological malignancies were included in the analysis. Among these studies, 13 were case reports or case series, two were retrospective in nature and two were observational studies.

The main haematological malignancies were follicular lymphoma, chronic lymphocytic leukaemia, non-Hodgkin’s lymphoma, diffused large B-cell lymphoma and B-cell lymphoma.

The dose of convalescent plasma ranged from 200 – 300 ml per transfusion and in many cases this therapy was used as the last option.

Mortality was the main clinical outcome reported in 21.7% of patients receiving CP and 25.2% in control patients. The use of CP was associated with an improved overall survival (odds ratio, OR = 1.41, 95% CI 0.99 – 1.99), viral clearance (OR = 2, 95% CI 1.04 – 2.08), detection of COVID-19 antibodies in the recipient’s plasma (OR = 6.33) and recovery one month after the use of CP (OR = 1.74, 95% CI 1.1 – 2.8).

The probability of developing an adverse effect in haematological malignancy patients was significantly reduced in those given CP compared to controls (OR = 0.24, 95% CI 0.14 – 0.40).

The authors concluded that CP was an effective and safe treatment for patients with haematological malignancies infected with COVID-19, adding that there was a need for further studies to provide a better understanding of the value of this intervention in cancer patients.

Citation
Shibeeb S et al. Effectiveness of convalescent plasma therapy in COVID-19 patients with haematological malignancies MedRxiv 2022

Haematological cancer patients at increased risk of severe breakthrough COVID-19 infections

22nd November 2021

Haematological cancer patients have been found to be at an increased risk of severe breakthrough COVID-19 infections

Haematological cancer patients are still at an increased risk of severe COVID-19 infections despite receiving two vaccination doses. This is according to a preliminary analysis of a disease register by researchers from Fondazione Policlinico Universitario Agostino Gemelli, Rome, Italy.

In April 2020, the European Haematological Association – infectious Diseases Working Party, established an open, web-based registry, EPICOVIDEHA. This was designed with a view to collecting information on the epidemiology, risk factors and mortality rates among patients with haematological cancer, who became infected with COVID-19. This was considered necessary given how patients with these malignancies and therefore a dysfunctional immune system are at an increased risk of complications if infected with COVID-19. Published data from the registry on 3801 patients has already shown a mortality rate of 31.2%, of whom, 58% died due to COVID-19 and 13.1% due to a combination of their malignancy and COVID-19.

However, since the introduction of COVID-19 vaccines, it is likely that the mortality rate would have been substantially lower. As a result, the Italian team prospectively collected registry data on adults who were either partially or fully vaccinated and who developed breakthrough COVID-19 infections, to assess the efficacy of the vaccines among those with haematological cancer. The register was used to capture data on the underlying condition of the patients before infection with COVID-19, their malignancy and vaccination status and details of their infection, e.g., disease severity, hospitalisation and mortality. They deemed fully vaccinated individuals as those form whom the second vaccine dose was administered 14 days before COVID-19 symptom onset or a positive PCR test result.

Findings

The researchers identified 113 patients with COVID-19 episodes and which occurred among both partially and fully vaccinated individuals with a haematological cancer. The median age of the patients was 66 years (61.1% male) and the most common malignancies were chronic lymphoid leukaemia (24.8%) and non-Hodgkin lymphoma (31.9%) and slightly more patients had active (53.1%) compared to controlled disease (45.1%) before infection with COVID-19. In addition, 87 (77%) of patients were fully vaccinated. From a subset of 40 of these fully vaccinated patients, only 13 (32.5%) had mounted an antibody response to vaccination with the remaining patients (67.5%) deemed non-responders.

Overall, 79 (60.4%) of haematological cancer patients had a severe COVID-19 infection, with 66.4% hospitalised and 21.3% admitted to an intensive care unit. Thirty days post-COVID-19 infection, the overall mortality rate was 12.4% (14 patients) and 10 of the 14 died due to their underlying malignancy. Interestingly, there were no differences in mortality between partially or fully vaccinated individuals (15.4% vs 11.5%, partial vs full vaccination, p = 0.73) or in terms of whether patients were considered as responders or non-responders to vaccination.

While the authors recognised that this was preliminary data, they are continuing to recruit haematological caner patients and will draw further conclusions once more data becomes available.

Citation

Pagano L et al. COVID-19 in vaccinated adult patients with hematological malignancies. Preliminary results from EPICOVIDEHA. Blood 2021.