Dr Lisa Hicks
Several studies presented at the ASH 21 meeting shed further light on the impact of COVID-19 on people with blood disorders, and advanced understanding of the related risk of serious illness or death, treatment and the efficacy of vaccination in these potentially vulnerable patient populations.
A key analysis of more than 1,000 patients in the ASH RC COVID-19 Registry for Haematology showed that patients with blood cancers were more at risk of death and serious illness from COVID-19 infection than the general population.
The study, led by Dr Lisa Hicks, a malignant haematologist at St. Michael’s Hospital in Toronto, Canada, included data from 1,029 patients around the globe, of which 34% had acute leukaemia or myelodysplastic syndromes (MDS), 25% had lymphoma, 20% had plasma cell dyscrasia, 11% had chronic lymphocytic leukaemia (CLL), and 10% had myeloproliferative neoplasm.
The analysis found that 17% of patients with blood cancers who had developed COVID-19 died from COVID-related illness, and that being of older age, male sex, having a poorer prognosis and a delay to receiving intensive care were all independent risk factors for death.
According to the data, terminally ill patients who were predicted to have less than six months to live because of their cancer were six times more likely to die from COVID than those with better prognoses, while for those delaying intensive care the risk of death was more than 10 times higher.
Reassuringly, though, having had cancer treatment in the prior year was not found to increase risk of death from COVID, but it did significantly raise the risk of hospitalisation.
Neutropenia, active disease linked to severe COVID
In a separate, retrospective analysis of 257 patients with acute leukaemia or MDS who developed COVID-19, neutropenia and having active MDS or leukaemia were independently linked to developing severe disease.
The research, led by Dr Pinkal Desai, from the Division of Haematology and Oncology at Weill Cornell Medical College in New York, US, was based on data from 135 patients with acute myeloid leukaemia (AML), 82 with acute lymphocytic leukaemia (ALL) and 40 with MDS.
Overall, 21% patients died from COVID-19, which the researchers noted was higher than the mortality rate reported for the entire ASH RC COVID-19 registry (17%) and that observed in the general public over the same time. The mortality rate among the study population hospitalised with COVID-related illness was 34%, and 68% among those admitted to intensive care.
Factors most strongly linked with risk of death were having an estimated survival time of less than six months due to the underlying haematological condition (odds ratio [OR] for death = 9) and deferring intensive care (OR = 7 versus 2 for those who didn’t defer intensive care).
Older age (OR = 2), male sex, and neutropenia at diagnosis (OR = 3 versus 2 for those without) were also linked with COVID-19 mortality, though to a lesser extent, but neither disease status nor ongoing cancer treatment had a significant affect on risk of mortality among hospitalised patients.
Elsewhere, two studies presented at ASH investigated antibody response following vaccination of people with haematologic malignancies, with one showing that some patients still have a high risk of developing COVID-19 post vaccination and the other detailing a strong antibody response to mRNA vaccination in patients with AML and MDS.
Negative antibody response in 15% of patients
Jil Rotterdam, from the Medizinische Klinik, Medizinische Fakultät Mannheim at the University of Heidelberg in Germany, and colleagues assessed the level of vaccine-related antibodies in 373 patients with blood disorders (91% malignant, 9% either autoimmune or non-malignant) around 12 weeks after their last dose.
While the majority (85%) developed vaccine-related antibodies, the data showed that a significant number of patients (15%) had not, potentially leaving them at greater risk of contracting SARS-CoV-2 (the study did not measure T-cell response to vaccination).
The research also revealed that within the group failing to achieve a vaccine response most had lymphoid neoplasms (60%), followed by myeloid neoplasms (26%) and non-malignant haematological disease (15%). Also, 78% were on active therapy, while 22% were previously treated or treatment naïve.
Strong vaccine response in people with AML, MDS
Dr Akriti Jain, from the Department of Malignant Haematology at the Moffitt Cancer Center in Florida, US, led an observational study in which antibody response to COVID-19 vaccination was measured in 46 people who had (67%)/were undergoing (33%) treatment for AML and MDS. Most patients (70%) in the trial had undergone a stem cell transplant from a healthy donor and 87% were in remission when vaccinated.
The authors said their data showed that 70% of patients had an antibody response 29 days after the first vaccination dose, and that, after 57 days and following the second dose, this “increased dramatically” to 97%.
According to the researchers, the seropositivity rate was not significantly affected by factors such as age, gender, race, disease activity, time between diagnosis and vaccination, previous lines of cancer therapy, and whether or not patients had received a stem cell transplant or were on active treatment when vaccinated.
The findings suggest potential utility for serial vaccination in poorly-responsive patients, the authors said, and concluded that while the results should be substantiated in a larger cohort, “mRNA-273 SARS-CoV-2 vaccine appears to induce a strong humoral response in this population of patients with AML and MDS”.
Vaccine efficacy after rituximab exposure
Research from the UK looked at vaccine responsiveness following exposure to B cell depleting agents, to build evidence on maximising vaccine efficacy in patients vulnerable to severe COVID-19.
The team, which included Dr Shankara Paneesha, Consultant Haematologist, University Hospitals Birmingham NHS Foundation Trust, assessed serological responsiveness to SARS-CoV-2 vaccines after a second dose in 80 patients with underlying haematological malignancy and 38 patients with underlying rheumatological disease previously treated with anti-CD20 B cell depleting agents.
In the haematology cohort, overall seropositivity following vaccination was 60.0%, and individuals on active chemotherapy had significantly lower seroprevalence than those vaccinated following the completion of chemotherapy (22.7% vs 74.1%, respectively). In the rheumatology cohort, overall seropositivity was 69.4%.
Response to the vaccine was lower in the first 6 months immediately after B cell depletion therapy – 42.9% in the haematology cohort and 33.3% in the rheumatology arm, however this rose to 100% and 75%, respectively, in people who received a second dose six to twelve months after B cell depletion.
The researchers also noted that B cell reconstitution in the 7-12 months following B cell depletion was much faster in haematology versus rheumatology patients (77.8% v 22.2% achieving normal B cell count) and was linked with improved vaccine responsiveness.
“However, persistent immunodeficiency occurred in some haematology patients following completion of treatment: 25% of patients who had completed therapy at least 36 months previously failed to respond to vaccination,” they said.
Benefit of less intensive chemo regimens?
Also in the UK, researchers including Dr Jenny O’Nions, a Haematology Consultant at University College London Hospitals NHS Foundation Trust, reported first data from the PACE trial, which looked at the impact of treatment regimens on COVID-19 infection rates in patients with AML/high risk MDS.
Overall, the incidence of COVID-19 infection for patients with AML/MDS-EB2 was 11.1%, and a lower proportion of patients (6.6%) undergoing non-intensive treatment developed the disease compared to those who were taking more intensive chemotherapy regimens (16.4%). Just 6.3% of patients who received a venetoclax regimen were infected with SARS-CoV2, the researchers noted.
The data showed a higher risk of death in patients with COVID-19 infection prior to or during treatment; the risk of death at 30 days after study entry in patients who had prior COVID-19 infection or who contracted the disease during the period was 13.6% compared to 3.9% in the overall cohort without COVID-19 infection.
“Venetoclax based, and other non-intensive, regimens, increasingly implemented during the pandemic, to minimise patient exposure and reduce usage of hospital beds, appeared to be associated with a low incidence of COVID-19. Further follow-up will be required to understand the long-term impact of this strategy,” the authors noted.