Registry sheds light on vulnerability of patients with hematologic malignancies, COVID-19
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Certain patients with hematologic malignancies and COVID-19 appeared at higher risk for severe infection and death, according to an analysis of data from an international registry presented at the virtual ASH Annual Meeting and Exposition.
The risk for death appeared highest among those who were older, had more severe infection, opted to forgo more intensive treatment and/or had a poorer cancer prognosis before COVID-19 infection, according to William A. Wood, MD, MPH, associate professor in the division of hematology/oncology at The University of North Carolina at Chapel Hill School of Medicine.
“In the early days of the COVID-19 pandemic, many hematologists were concerned that our patients could be at increased risk for adverse outcomes from COVID-19 infection for a variety of reasons — many of our patients are older, have underlying or treatment-induced comorbidities, have immune dysregulation or treatment-related immunosuppression and may already be susceptible to COVID-19 infection-related complications, such as thrombosis,” Wood, who also serves as a HemOnc Today Editorial Board Member, told Healio. “With this in mind, the ASH Research Collaborative facilitated the development of a COVID-19 registry.”
Launched in April, the ASH Research Collaborative COVID-19 Registry for Hematology includes voluntary contributions of clinical data from more than 100 international study sites. Researchers can aggregate de-identified data and make the results available to clinicians in near-real time, Wood added.
For the study, investigators pooled data from the registry on 656 patients (77% aged 40 years or older; 60% men; 43% white) with various hematologic malignancies and laboratory-confirmed or presumptive diagnosis of COVID-19 infection. Among them, 57% had comorbidities reported, the most common of which included hypertension (50%) and diabetes (30%). More than half (57%) had leukemia, 25% had lymphoma and 18% had plasma cell neoplasms. Most (80%) had an expected survival of more than 12 months prior to COVID-19 infection.
The most common COVID-19-associated symptoms included fever (65%), cough (56%), dyspnea (39%) and fatigue (31%), whereas 11% reported no symptoms. Most patients received COVID-19-directed therapies, including azithromycin (n = 143), hydroxychloroquine (n = 137), convalescent plasma (n = 45) and remdesivir (Veklury, Gilead Sciences; n = 44).
Overall, 20% of patients died during the study period between April and November, including 33% of those who required hospital-level or ICU-level care. The mortality rate among those with ICU-level care was 65%.
Similar percentages (61% to 65%) of patients with leukemia, lymphoma or plasma cell disorders had moderate or severe COVID-19, Wood added.
COVID-19 severity was strongly correlated with malignancy status at the time of diagnosis, with 69% of those receiving initial treatment for a hematologic malignancy having moderate or severe disease compared with 50% in remission and 79% with relapsed or refractory disease.
Overall, 62% of patients with known severity status had moderate or severe COVID-19 infection. Among those aged younger than 19 years, 47% had moderate or severe disease, compared with 43% of those aged 19 to 39 years, 62% of those aged 40 to 69 years and 70% of those aged 70 years or older. The choice to forgo ICU care was strongly associated with age, with a 73% mortality rate among those who declined ICU-level care compared with 13% among those who did not.
Mortality rates differed significantly by prognosis. More than half (51%) of patients with pre-COVID-19 expected survival of less than 12 months died compared with 13% of patients with expected survival of more than 12 months. Mortality rates also differed significantly by malignancy status, with 21% mortality among those receiving initial treatment, 13% among those in remission and 36% among those with relapsed or refractory disease.
“Our findings suggest that patients with hematologic malignancies are a medically vulnerable group when it comes to COVID-19 infection,” Wood said. “It is therefore important for these patients and for the health care system to continue to take appropriate precautions to limit the risk [for] acquiring COVID-19.”
At the same time, most patients in study who acquired COVID-19 infection — and several who had severe disease and required ICU-level care — survived, Wood added.
“Thus, providing maximal care to patients with hematologic malignancies and COVID-19 infection appears appropriate if it is consistent with patient and family preferences. As the data mature, the registry may be able to better inform specific risks from specific treatments and specific underlying diseases, which could have an impact upon treatment decision-making,” he said.
The registry’s reliance on voluntary reporting, resulting in estimates that may not be the same as from a true population-based registry, served as a limitation of the study, according to Wood.
“This highlights the need for enhanced data-collection systems involving patients with underlying hematologic diseases,” he added. “The ASH Research Collaborative Data Hub is building programs that will help to address this gap, starting with sickle cell disease and multiple myeloma, and expanding to other diseases in the future. In the meantime, we encourage continued data collection to the ASH Research Collaborative COVID-19 Registry from hematologists around the world, so that the data resource we are building can be used to address further questions about COVID-19 and cancer that are relevant to hematologists. We encourage anyone who is interested to visit www.ashrc.org to learn more about the COVID-19 registry, view data summaries and, importantly, to contribute data.”
Perspective
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When giving aggressive therapy to treat and cure some of these aggressive hematologic cancers, patients become neutropenic. Having neutropenia and then becoming infected with COVID-19 is almost always fatal. Still, even outside of neutropenic episodes, these patients are immunocompromised because of their underlying hematologic cancer. Because they have low lymphocyte counts, their viral phase gets overwhelmed and they often die due to progression of COVID-19.
We found that by tweaking some maintenance treatments, we were able to protect some of our patients with hematologic malignancies. But, there is a fine line between this mitigation and dealing with patients undergoing treatment for refractory disease, as they have a much higher risk for mortality compared with patients who are in remission from their cancer.
The same treatments used for patients with hematologic malignancies and COVID-19 are given to other noncancer patients, except we have given our patients with hematologic cancers convalescent plasma with higher titers. We also check the antibody to validate that it blocks the virus in vitro, and we have an ongoing study looking into this now.
During the COVID-19 pandemic, we have seen later diagnoses because patients are afraid to come to the doctor, which leads to delayed diagnosis and stage migration in lymphomas. We will continue to see stage migration in oncology overall, especially for solid tumors because hematologic cancers are more symptomatic, so they get diagnosed. We also will see a dramatic increase in indirect mortality. Every state has seen a huge increase in sudden death, where people are dying at home without a clear diagnosis. This is not to say that these deaths are associated with COVID-19, but these are patients who had other symptoms and did not seek medical care. This will be a significant issue across the board, not only in oncology, moving forward.
These data from Wood and colleagues resonate with other data presented at ASH this year on AML outcomes among minorities, which showed that although complete remission rates were not significantly different between races, outcomes were significantly worse among Blacks. This has to do with comorbidities and social determinants of health. COVID-19 is an amplifier of social determinants of health because people are more confined to the home, where situations are difficult regarding access to care and several other social factors. This illustrates a number of critical issues that are emerging in our society that we as health care providers must tackle.
Hackensack University Medical Center
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Andrew Ip, MD
This is a massive effort that Wood and colleagues have conducted across various institutions. We have had very similar outcomes in our database, as well. For example, 33% of hospitalized patients in their study died, which is very similar to what has been reported elsewhere and reported in our database. It is important to note that this was conducted during a 6- to 7-month period, and likely the mortality rates were much higher in April and May than within the last couple of months, for varying reasons. This is something that we need to keep in mind when looking at registries spanning the COVID-19 pandemic, as Wood and colleagues will most likely adjust for time-varying confounding in the final paper that they may publish on this.
We have tried to attack COVID-19 with convalescent high-titer plasma for a lot of our patients with hematologic cancer because they are immunosuppressed or are B-cell depleted due to different chemotherapies. Researchers for this study used this treatment in about 45 patients, which seems to be a small number, given that 65% of these patients (approximately 450 of the 700) in their registry were classified as having moderate or severe COVID-19 infection. At our cancer center, we are giving convalescent plasma to all of our hospitalized patients and to many of our patients with mild COVID-19 who are still recovering at home as outpatients.
The way different centers are treating COVID-19 is variable because no one really knows what to do. We do not yet have great randomized data on convalescent plasma, but at our center we have seen some of the initial positive results, which our colleagues here will soon be publishing and have moved on to a larger randomized study.
Although these data reflect what went on early in the pandemic, things are moving so rapidly with the virus. Hopefully in the future, this registry will add more interesting analyses as they collect more nuanced and complex data.
Hackensack University Medical Center
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Wood WA, et al. Abstract 215. Presented at: ASH Annual Meeting and Exposition (virtual meeting); Dec. 5-8, 2020.
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