Dexamethasone treatment for COVID-19 is related to increased mortality in hematologic malignancy patients: results from the EPICOVIDEHA Registry.

Not available.

Reducing and controlling metabolic active tumor volume prior to CAR T-cell infusion can improve survival outcomes in patients with large B-cell lymphoma.

Bridging therapy before CD19-directed chimeric antigen receptor (CAR) T-cell infusion is frequently applied in patients with relapsed or refractory Large B-cell lymphoma (r/r LBCL). This study aimed to assess the influence of quantified MATV and MATV-dynamics, between pre-apheresis (baseline) and pre-lymphodepleting chemotherapy (pre-LD) MATV, on CAR T-cell outcomes and toxicities in patients with r/r LBCL. MATVs were calculated semi-automatically at baseline (n = 74) and pre-LD (n = 68) in patients with r/r LBCL who received axicabtagene ciloleucel. At baseline, patients with a low MATV (< 190 cc) had a better time to progression (TTP) and overall survival (OS) compared to high MATV patients (p < 0.001). High MATV patients who remained stable or reduced upon bridging therapy showed a significant improvement in TTP (p = 0.041) and OS (p = 0.015), compared to patients with a high pre-LD MATV (> 480 cc). Furthermore, high MATV baseline was associated with severe cytokine release syndrome (CRS, p = 0.001). In conclusion, patients with low baseline MATV had the best TTP/OS and effective reduction or controlling MATV during bridging improved survival outcomes in patients with a high baseline MATV, providing rationale for the use of more aggressive bridging regimens.

Decoding the historical tale: COVID-19 impact on haematological malignancy patients-EPICOVIDEHA insights from 2020 to 2022.

Background: The COVID-19 pandemic heightened risks for individuals with hematological malignancies due to compromised immune systems, leading to more severe outcomes and increased mortality. While interventions like vaccines, targeted antivirals, and monoclonal antibodies have been effective for the general population, their benefits for these patients may not be as pronounced. Methods: The EPICOVIDEHA registry (National Clinical Trials Identifier, NCT04733729) gathers COVID-19 data from hematological malignancy patients since the pandemic's start worldwide. It spans various global locations, allowing comprehensive analysis over the first three years (2020-2022). Findings: The EPICOVIDEHA registry collected data from January 2020 to December 2022, involving 8767 COVID-19 cases in hematological malignancy patients from 152 centers across 41 countries, with 42% being female. Over this period, there was a significant reduction in critical infections and an overall decrease in mortality from 29% to 4%. However, hospitalization, particularly in the ICU, remained associated with higher mortality rates. Factors contributing to increased mortality included age, multiple comorbidities, active malignancy at COVID-19 onset, pulmonary symptoms, and hospitalization. On the positive side, vaccination with one to two doses or three or more doses, as well as encountering COVID-19 in 2022, were associated with improved survival. Interpretation: Patients with hematological malignancies still face elevated risks, despite reductions in critical infections and overall mortality rates over time. Hospitalization, especially in ICUs, remains a significant concern. The study underscores the importance of vaccination and the timing of COVID-19 exposure in 2022 for enhanced survival in this patient group. Ongoing monitoring and targeted interventions are essential to support this vulnerable population, emphasizing the critical role of timely diagnosis and prompt treatment in preventing severe COVID-19 cases. Funding: Not applicable.

Survival in multiple myeloma and SARS-COV-2 infection through the COVID-19 pandemic: Results from the EPICOVIDEHA registry.

Patients affected by multiple myeloma (MM) have an increased risk of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection and subsequent coronavirus (20)19 disease (COVID-19)-related death. The changing epidemiological and therapeutic scenarios suggest that there has been an improvement in severity and survival of COVID-19 during the different waves of the pandemic in the general population, but this has not been investigated yet in MM patients. Here we analyzed a large cohort of 1221 patients with MM and confirmed SARS-CoV-2 infection observed between February 2020, and August 2022, in the EPICOVIDEHA registry from 132 centers around the world. Median follow-up was 52 days for the entire cohort and 83 days for survivors. Three-hundred and three patients died (24%) and COVID-19 was the primary reason for death of around 89% of them. Overall survival (OS) was significantly higher in vaccinated patients with both stable and active MM versus unvaccinated, while only a trend favoring vaccinated patients was observed in subjects with responsive MM. Vaccinated patients with at least 2 doses showed a better OS than those with one or no vaccine dose. Overall, according to pandemic waves, mortality rate decreased over time from 34% to 10%. In multivariable analysis, age, renal failure, active disease, hospital, and intensive care unit admission, were independently associated with a higher number of deaths, while a neutrophil count above 0.5 × 109 /L was found to be protective. This data suggests that MM patients remain at risk of SARS-CoV-2 infection even in the vaccination era, but their clinical outcome, in terms of OS, has progressively improved throughout the different viral phases of the pandemic.

The mortality of COVID-19 in CML patients from 2020 until 2022: results from the EPICOVIDEHA survey.

Since the beginning of the COVID-19 pandemic, there has been an overall improvement in patient mortality. However, haematological malignancy patients continue to experience significant impacts from COVID-19, including high rates of hospitalization, intensive care unit (ICU) admissions, and mortality. In comparison to other haematological malignancy patients, individuals with chronic myeloid leukemia (CML) generally have better prognosis. This study, conducted using a large haematological malignancy patient database (EPICOVIDEHA), demonstrated that the majority of CML patients experienced mild infections. The decline in severe and critical infections over the years can largely be attributed to the widespread administration of vaccinations and the positive response they elicited. Notably, the mortality rate among CML patients was low and exhibited a downward trend in subsequent years. Importantly, our analysis provided confirmation of the effectiveness of vaccinations in CML patients.

Population-Based External Validation of the EASIX Scores to Predict CAR T-Cell-Related Toxicities.

Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) can hamper the clinical benefit of CAR T-cell therapy in patients with relapsed/refractory large B-cell lymphoma (r/r LBCL). To assess the risk of CRS and ICANS, the endothelial activation and stress index (EASIX), the modified EASIX (m-EASIX), simplified EASIX (s-EASIX), and EASIX with CRP/ferritin (EASIX-F(C)) were proposed. This study validates these scores in a consecutive population-based cohort. Patients with r/r LBCL treated with axicabtagene ciloleucel were included (n = 154). EASIX scores were calculated at baseline, before lymphodepletion (pre-LD) and at CAR T-cell infusion. The EASIX and the s-EASIX at pre-LD were significantly associated with ICANS grade ≥ 2 (both p = 0.04), and the EASIX approached statistical significance at infusion (p = 0.05). However, the predictive performance was moderate, with area under the curves of 0.61-0.62. Validation of the EASIX-FC revealed that patients in the intermediate risk group had an increased risk of ICANS grade ≥ 2 compared to low-risk patients. No significant associations between EASIX scores and CRS/ICANS grade ≥ 3 were found. The (m-/s-) EASIX can be used to assess the risk of ICANS grade ≥ 2 in patients treated with CAR T-cell therapy. However, due to the moderate performance of the scores, further optimization needs to be performed before broad implementation as a clinical tool, directing early intervention and guiding outpatient CAR T-cell treatment.

Age, successive waves, immunization, and mortality in elderly COVID-19 hematological patients: EPICOVIDEHA findings.

OBJECTIVES: Elderly patients with hematologic malignancies face the highest risk of severe COVID-19 outcomes. The infection's impact on different age groups remains unstudied in detail. METHODS: We analyzed elderly patients (age groups: 65-70, 71-75, 76-80, and >80 years old) with hematologic malignancies included in the EPICOVIDEHA registry between January 2020 and July 2022. Univariable and multivariable Cox regression models were conducted to identify factors influencing death in COVID-19 patients with hematological malignancy. RESULTS: The study included data from 3,603 elderly patients (aged 65 or older) with hematological malignancy, with a majority being male (58.1%) and a significant proportion having comorbidities. The patients were divided into four age groups, and the analysis assessed COVID-19 outcomes, vaccination status, and other variables in relation to age and pandemic waves. The 90-day survival rate for patients with COVID-19 was 71.2%, with significant differences between groups. The pandemic waves had varying impacts, with the first wave affecting patients over 80 years old, the second being more severe in 65-70, and the third being the least severe in all age groups. Factors contributing to 90-day mortality included age, comorbidities, lymphopenia, active malignancy, acute leukemia, less than three vaccine doses, severe COVID-19, and using only corticosteroids as treatment. CONCLUSION: These data underscore the heterogeneity of elderly hematological patients, highlight the different impacts of COVID-19 waves and the pivotal importance of vaccination, and may help in planning future healthcare efforts.

The Dutch CAR-T Tumorboard Experience: Population-Based Real-World Data on Patients with Relapsed or Refractory Large B-Cell Lymphoma Referred for CD19-Directed CAR T-Cell Therapy in The Netherlands.

The real-world results of chimeric antigen receptor T-cell (CAR-T) therapy for patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL) substantially differ across countries. In the Netherlands, the CAR-T tumorboard facilitates a unique nationwide infrastructure for referral, eligibility assessment and data collection. The aim of this study was to evaluate real-world outcomes of axicabtagene ciloleucel (axi-cel) in the Dutch population, including the thus-far underreported effects on health-related quality of life (HR-QoL). All patients with R/R LBCL after ≥2 lines of systemic therapy referred for axi-cel treatment between May 2020-May 2022 were included (N = 250). Of the 160 apheresed patients, 145 patients received an axi-cel infusion. The main reason for ineligibility was rapidly progressive disease. The outcomes are better or at least comparable to other studies (best overall response rate: 84% (complete response: 66%); 12-month progression-free-survival rate and overall survival rate: 48% and 62%, respectively). The 12-month NRM was 5%, mainly caused by infections. Clinically meaningful improvement in several HR-QoL domains was observed from Month 9 onwards. Expert-directed patient selection can support effective and sustainable application of CAR-T treatment. Matched comparisons between cohorts will help to understand the differences in outcomes across countries and select best practices. Despite the favorable results, for a considerable proportion of patients with R/R LBCL there still is an unmet medical need.

Fourth mRNA COVID-19 vaccination in immunocompromised patients with haematological malignancies (COBRA KAI): a cohort study.

Background: Patients with haematological malignancies have impaired antibody responses to SARS-CoV-2 vaccination. We aimed to investigate whether a fourth mRNA COVID-19 vaccination improved antibody quantity and quality. Methods: In this cohort study, conducted at 5 sites in the Netherlands, we compared antibody concentrations 28 days after 4 mRNA vaccinations (3-dose primary series plus 1 booster vaccination) in SARS-CoV-2 naive, immunocompromised patients with haematological malignancies to those obtained by age-matched, healthy individuals who had received the standard primary 2-dose mRNA vaccination schedule followed by a first booster mRNA vaccination. Prior to and 4 weeks after each vaccination, peripheral blood samples and data on demographic parameters and medical history were collected. Concentrations of antibodies that bind spike 1 (S1) and nucleocapsid (N) protein of SARS-CoV-2 were quantified in binding antibody units (BAU) per mL according to the WHO International Standard for COVID-19 serological tests. Seroconversion was defined as an S1 IgG concentration >10 BAU/mL and a previous SARS-CoV-2 infection as N IgG >14.3 BAU/mL. Antibody neutralising activity was tested using lentiviral-based pseudoviruses expressing spike protein of SARS-CoV-2 wild-type (D614G), Omicron BA.1, and Omicron BA.4/5 variants. This study is registered with EudraCT, number 2021-001072-41. Findings: Between March 24, 2021 and May 4, 2021, 723 patients with haematological diseases were enrolled, of which 414 fulfilled the inclusion criteria for the current analysis. Although S1 IgG concentrations in patients significantly improved after the fourth dose, they remained significantly lower compared to those obtained by 58 age-matched healthy individuals after their first booster (third) vaccination. The rise in neutralising antibody concentration was most prominent in patients with a recovering B cell compartment, although potent responses were also observed in patients with persistent immunodeficiencies. 19% of patients never seroconverted, despite 4 vaccinations. Patients who received their first 2 vaccinations when they were B cell depleted and the third and fourth vaccination during B cell recovery demonstrated similar antibody induction dynamics as patients with normal B cell numbers during the first 2 vaccinations. However, the neutralising capacity of these antibodies was significantly better than that of patients with normal B cell numbers after two vaccinations. Interpretation: A fourth mRNA COVID-19 vaccination improved S1 IgG concentrations in the majority of patients with a haematological malignancy. Vaccination during B cell depletion may pave the way for better quality of antibody responses after B cell reconstitution. Funding: The Netherlands Organisation for Health Research and Development and Amsterdam UMC.

Nirmatrelvir/ritonavir in COVID-19 patients with haematological malignancies: a report from the EPICOVIDEHA registry.

Background: Nirmatrelvir/ritonavir treatment decreases the hospitalisation rate in immunocompetent patients with COVID-19, but data on efficacy in patients with haematological malignancy are scarce. Here, we describe the outcome of nirmatrelvir/ritonavir treatment in a large cohort of the latter patients. Methods: This is a retrospective cohort study from the multicentre EPICOVIDEHA registry (NCT04733729) on patients with haematological malignancy, who were diagnosed with COVID-19 between January and September 2022. Patients receiving nirmatrelvir/ritonavir were compared to those who did not. A logistic regression was run to determine factors associated with nirmatrelvir/ritonavir administration in our sample. Mortality between treatment groups was assessed with Kaplan-Meier survival plots after matching all the patients with a propensity score. Additionally, a Cox regression was modelled to detect factors associated with mortality in patients receiving nirmatrelvir/ritonavir. Findings: A total of 1859 patients were analysed, 117 (6%) were treated with nirmatrelvir/ritonavir, 1742 (94%) were treated otherwise. Of 117 patients receiving nirmatrelvir/ritonavir, 80% had received ≥1 anti-SARS-CoV-2 vaccine dose before COVID-19 onset, 13% of which received a 2nd vaccine booster. 5% were admitted to ICU. Nirmatrelvir/ritonavir treatment was associated with the presence of extrapulmonary symptoms at COVID-19 onset, for example anosmia, fever, rhinitis, or sinusitis (aOR 2.509, 95%CI 1.448-4.347) and 2nd vaccine booster (aOR 3.624, 95%CI 1.619-8.109). Chronic pulmonary disease (aOR 0.261, 95%CI 0.093-0.732) and obesity (aOR 0.105, 95%CI 0.014-0.776) were not associated with nirmatrelvir/ritonavir use. After propensity score matching, day-30 mortality rate in patients treated with nirmatrelvir/ritonavir was 2%, significantly lower than in patients with SARS-CoV-2 directed treatment other than nirmatrelvir/ritonavir (11%, p = 0.036). No factor was observed explaining the mortality difference in patients after nirmatrelvir/ritonavir administration. Interpretation: Haematological malignancy patients were more likely to receive nirmatrelvir/ritonavir when reporting extrapulmonary symptoms or 2nd vaccine booster at COVID-19 onset, as opposed to chronic pulmonary disease and obesity. The mortality rate in patients treated with nirmatrelvir/ritonavir was lower than in patients with targeted drugs other than nirmatrelvir/ritonavir. Funding: EPICOVIDEHA has received funds from Optics COMMIT (COVID-19 Unmet Medical Needs and Associated Research Extension) COVID-19 RFP program by GILEAD Science, United States (Project 2020-8223).

Passive pre-exposure immunization by tixagevimab/cilgavimab in patients with hematological malignancy and COVID-19: matched-paired analysis in the EPICOVIDEHA registry.

Only few studies have analyzed the efficacy of tixagevimab/cilgavimab to prevent severe Coronavirus disease 2019 (COVID-19) and related complications in hematologic malignancies (HM) patients. Here, we report cases of breakthrough COVID-19 after prophylactic tixagevimab/cilgavimab from the EPICOVIDEHA registry). We identified 47 patients that had received prophylaxis with tixagevimab/cilgavimab in the EPICOVIDEHA registry. Lymphoproliferative disorders (44/47, 93.6%) were the main underlying HM. SARS-CoV-2 strains were genotyped in 7 (14.9%) cases only, and all belonged to the omicron variant. Forty (85.1%) patients had received vaccinations prior to tixagevimab/cilgavimab, the majority of them with at least two doses. Eleven (23.4%) patients had a mild SARS-CoV-2 infection, 21 (44.7%) a moderate infection, while 8 (17.0%) had severe infection and 2 (4.3%) critical. Thirty-six (76.6%) patients were treated, either with monoclonal antibodies, antivirals, corticosteroids, or with combination schemes. Overall, 10 (21.3%) were admitted to a hospital. Among these, two (4.3%) were transferred to intensive care unit and one (2.1%) of them died. Our data seem to show that the use of tixagevimab/cilgavimab may lead to a COVID-19 severity reduction in HM patients; however, further studies should incorporate further HM patients to confirm the best drug administration strategies in immunocompromised patients.

Impact of SARS-CoV-2 vaccination and monoclonal antibodies on outcome post-CD19-directed CAR T-cell therapy: an EPICOVIDEHA survey.

Patients with previous CD19-directed chimeric antigen receptor (CAR) T-cell therapy have a prolonged vulnerability to viral infections. Coronavirus disease 2019 (COVID-19) has a great impact and has previously been shown to cause high mortality in this population. Until now, real-world data on the impact of vaccination and treatment on patients with COVID-19 after CD19-directed CAR T-cell therapy are lacking. Therefore, this multicenter, retrospective study was conducted with data from the EPICOVIDEHA survey. Sixty-four patients were identified. The overall mortality caused by COVID-19 was 31%. Patients infected with the Omicron variant had a significantly lower risk of death due to COVID-19 compared with patients infected with previous variants (7% vs 58% [P = .012]). Twenty-six patients were vaccinated at the time of the COVID-19 diagnosis. Two vaccinations showed a marked but unsignificant reduction in the risk of COVID-19-caused mortality (33.3% vs 14.2% [P = .379]). In addition, the course of the disease appears milder with less frequent intensive care unit admissions (39% vs 14% [P = .054]) and a shorter duration of hospitalization (7 vs 27.5 days [P = .022]). Of the available treatment options, only monoclonal antibodies seemed to be effective at reducing mortality from 32% to 0% (P = .036). We conclude that survival rates of CAR T-cell recipients with COVID-19 improved over time and that the combination of prior vaccination and monoclonal antibody treatment significantly reduces their risk of death. This trial was registered at www.clinicaltrials.gov as #NCT04733729.

Outcome of COVID-19 in allogeneic stem cell transplant recipients: Results from the EPICOVIDEHA registry.

Background: The outcome of COVID-19 in allogeneic hematopoietic stem cell transplantation (HSCT) recipients is almost uniformely considered poor. The aim of present study was to retrospectively analyse the outcome and risk factors for mortality in a large series of patients who developed COVID-19 infection after an allogeneic HSCT. Methods: This multicenter retrospective study promoted by the European Hematology Association - Infections in Hematology Study Working Group, included 326 adult HSCT patients who had COVID-19 between January 2020 and March 2022. Results: The median time from HSCT to the diagnosis of COVID-19 was 268 days (IQR 86-713; range 0-185 days). COVID-19 severity was mild in 21% of the patients, severe in 39% and critical in 16% of the patients. In multivariable analysis factors associated with a higher risk of mortality were, age above 50 years, presence of 3 or more comorbidities, active hematologic disease at time of COVID-19 infection, development of COVID-19 within 12 months of HSCT, and severe/critical infections. Overall mortality rate was 21% (n=68): COVID-19 was the main or secondary cause of death in 16% of the patients (n=53). Conclusions: Mortality in HSCT recipients who develop COVID-19 is high and largely dependent on age, comorbidities, active hematologic disease, timing from transplant and severity of the infection.

Outcomes of SARS-CoV-2 infection in Ph-neg chronic myeloproliferative neoplasms: results from the EPICOVIDEHA registry.

Background: Patients with Philadelphia-negative chronic myeloproliferative neoplasms (MPN) typically incur high rates of infections and both drugs and comorbidities may modulate infection risk. Objectives: The present study aims to assess the effect of immunosuppressive agents on clinical outcomes of MPN patients affected by the coronavirus disease 2019 (COVID-19). Design: This is an observational study. Methods: We specifically searched and analyzed MPN patients collected by EPICOVIDEHA online registry, which includes individuals with hematological malignancies diagnosed with COVID-19 since February 2020. Results: Overall, 398 patients with MPN were observed for a median of 76 days [interquartile range (IQR): 19-197] after detection of SARS-CoV2 infection. Median age was 69 years (IQR: 58-77) and 183 individuals (46%) had myelofibrosis (MF). Overall, 121 patients (30%) of the whole cohort received immunosuppressive therapies including steroids, immunomodulatory drugs, or JAK inhibitors. Hospitalization and consecutive admission to intensive care unit was required in 216 (54%) and 53 patients (13%), respectively. Risk factors for hospital admission were identified by multivariable logistic regression and include exposure to immunosuppressive therapies [odds ratio (OR): 2.186; 95% confidence interval (CI): 1.357-3.519], age ⩾70 years, and comorbidities. The fatality rate was 22% overall and the risk of death was independently increased by age ⩾70 years [hazard ratio (HR): 2.191; 95% CI: 1.363-3.521], previous comorbidities, and exposure to immunosuppressive therapies before the infection (HR: 2.143; 95% CI: 1.363-3.521). Conclusion: COVID-19 infection led to a particularly dismal outcome in MPN patients receiving immunosuppressive agents or reporting multiple comorbidities. Therefore, specific preventive strategies need to be tailored for such individuals. Plain language summary: EPICOVIDEHA registry reports inferior outcomes of COVID-19 in patients with Philadelphia-negative chronic myeloproliferative neoplasms receiving immunosuppressive therapies. Patients with Philadelphia-negative chronic myeloproliferative neoplasms (MPN) incur high rates of infections during the course of their disease.The present study was aimed at assessing which patient characteristics predicted a worse outcome of SARS-COV-2 infection in individuals with MPN.To pursue this objective, the researchers analyzed the data collected by EPICOVIDEHA, an international online registry, which includes individuals with hematological malignancies diagnosed with COVID-19 since February 2020.The database provided clinical data of 398 patients with MPN incurring COVID-19:Patients were mostly elderly (median age was 69 years);Forty-six percent of them were affected by myelofibrosis, which is the most severe MPN;Moreover, 32% were receiving immunosuppressive therapies (JAK inhibitors, such as ruxolitinib, steroids, or immunomodulatory IMID drugs, such as thalidomide) before COVID-19.Hospitalization was required in 54% of the patients, and the risk of being hospitalized for severe COVID-19 was independently predicted byOlder age;Comorbidities;Exposure to immunosuppressive therapies.Overall, 22% of MPN patients deceased soon after COVID-19 and the risk of death was independently increased over twofold byOlder age;Comorbidities;Exposure to immunosuppressive therapies before the infection.In conclusion, COVID-19 infection led to a particularly dismal outcome in MPN patients receiving immunosuppressive agents, including JAK inhibitors, or reporting multiple comorbidities. Therefore, specific preventive strategies need to be tailored for such individuals.

Semi-automated 18F-FDG PET segmentation methods for tumor volume determination in Non-Hodgkin lymphoma patients: a literature review, implementation and multi-threshold evaluation.

In the treatment of Non-Hodgkin lymphoma (NHL), multiple therapeutic options are available. Improving outcome predictions are essential to optimize treatment. The metabolic active tumor volume (MATV) has shown to be a prognostic factor in NHL. It is usually retrieved using semi-automated thresholding methods based on standardized uptake values (SUV), calculated from 18F-Fluorodeoxyglucose Positron Emission Tomography (18F-FDG PET) images. However, there is currently no consensus method for NHL. The aim of this study was to review literature on different segmentation methods used, and to evaluate selected methods by using an in house created software tool. A software tool, MUltiple SUV Threshold (MUST)-segmenter was developed where tumor locations are identified by placing seed-points on the PET images, followed by subsequent region growing. Based on a literature review, 9 SUV thresholding methods were selected and MATVs were extracted. The MUST-segmenter was utilized in a cohort of 68 patients with NHL. Differences in MATVs were assessed with paired t-tests, and correlations and distributions figures. High variability and significant differences between the MATVs based on different segmentation methods (p < 0.05) were observed in the NHL patients. Median MATVs ranged from 35 to 211 cc. No consensus for determining MATV is available based on the literature. Using the MUST-segmenter with 9 selected SUV thresholding methods, we demonstrated a large and significant variation in MATVs. Identifying the most optimal segmentation method for patients with NHL is essential to further improve predictions of toxicity, response, and treatment outcomes, which can be facilitated by the MUST-segmenter.

COVID-19 in adult acute myeloid leukemia patients: a long-term follow-up study from the European Hematology Association survey (EPICOVIDEHA).

Patients with acute myeloid leukemia (AML) are at high risk of dying from coronavirus disease 2019 (COVID-19). The optimal management of AML patients with COVID-19 has not been established. Our multicenter study included 388 adult AML patients diagnosed with COVID-19 between February 2020 and October 2021. The vast majority were receiving or had received AML treatment in the preceding 3 months. COVID-19 was severe in 41.2% and critical in 21.1% of cases. The chemotherapeutic schedule was modified in 174 patients (44.8%), delayed in 68 and permanently discontinued in 106. After a median follow-up of 325 days, 180 patients (46.4%) had died; death was attributed to COVID-19 (43.3%), AML (26.1%) or to a combination of both (26.7%), whereas in 3.9% of cases the reason was unknown. Active disease, older age, and treatment discontinuation were associated with death, whereas AML treatment delay was protective. Seventy-nine patients had a simultaneous AML and COVID-19 diagnosis, with better survival when AML treatment could be delayed (80%; P<0.001). Overall survival in patients with a diagnosis of COVID-19 between January 2020 and August 2020 was significantly lower than that in patients diagnosed between September 2020 and February 2021 and between March 2021 and September 2021 (39.8% vs. 60% vs. 61.9%, respectively; P=0.006). COVID-19 in AML patients was associated with a high mortality rate and modifications of therapeutic algorithms. The best approach to improve survival was to delay AML treatment, whenever possible.

Development of a Core Set of Patient- and Caregiver-Reported Signs and Symptoms to Facilitate Early Recognition of Acute Chimeric Antigen Receptor T-Cell Therapy Toxicities.

PURPOSE: Prompt recognition of acute chimeric antigen receptor T (CAR T)-cell-mediated toxicities is crucial because adequate and timely management can prevent or reverse potential life-threatening complications. In the outpatient setting, patients and informal caregivers have to recognize and report signs and symptoms marking these acute toxicities. This study provides a core set of patient- and caregiver-reported signs and symptoms (outcomes, P/CROs) and definitions of red flags warranting immediate action to include in a daily checklist for support at home, with the goal to make outpatient post-CAR T-cell care safer, optimize patient and caregiver support, and thereby facilitating an early discharge/hospital visit reduction strategy. METHODS: We performed a systematic review of phase II/III trials of US Food and Drug Administration-approved CAR T-cell products and selected all common and severe adverse events that could be translated into a P/CRO for inclusion in a two-round modified Delphi procedure. Eleven CAR T-cell-dedicated hematologists from the Dutch CAR T-cell tumorboard representing all treating centers selected P/CROs for inclusion in the core set and defined red flags. The final core set was evaluated with patients and caregivers. RESULTS: From nine clinical trials, 457 adverse events were identified of which 42 could be used as P/CRO. The final core set contains 28 items, including five signs for measurement via wearables and two signs for caregiver-performed assessments. CONCLUSION: This study provides a core set of P/CROs that can serve as a framework for (eHealth) tools that aim to enable patients and caregivers to more effectively recognize and report signs and symptoms of acute toxicities after CAR T-cell therapy, which will enhance safe outpatient treatment monitoring.