Pooled analysis of first-line treatment with targeted agents in patients with chronic lymphocytic leukemia aged 80 years and older.

Patients aged 80 years and older make up a fifth of patients with CLL but are underrepresented in clinical trials. We analyzed the outcomes of these patients treated with targeted agents in the front-line setting in six trials of the German CLL Study Group. Targeted agents included venetoclax, ibrutinib, and idelalisib, mainly used in combination with anti-CD20 antibodies. Among 716 patients, 33 matched the selection criteria (5%). Of those, the majority had relevant comorbidity, organ dysfunctions, and/or high-/very high-risk disease. The overall response rate was 73%. The median progression-free survival was 49.2 months compared with those not reached in younger patients. There were 11 documented deaths of which two were deemed related to therapy. Additional results including 40 patients treated with BTK-inhibitors from the GCLLSG registry suggest that treatment with targeted agents is feasible and effective. Dedicated studies are warranted for this particular subgroup of patients.

Cancer care in German centers of excellence during the first 2 years of the COVID-19 pandemic.

PURPOSE: An increasing number of international studies demonstrate serious negative effects of the COVID-19 pandemic on the timely diagnosis of cancer and on cancer treatment. Our study aimed to quantitatively and qualitatively evaluate the capacities of German Comprehensive Cancer Centers (CCCs) in different areas of complex oncology care during the first 2 years of the COVID-19 pandemic. METHODS: Prospective panel survey over 23 rounds among 18 CCCs in Germany between March 2020 and June 2022. RESULTS: The COVID-19 pandemic substantially affected the oncological care system in Germany during the first 2 years. Persistent limitations of care in CCCs primarily affected follow-up (- 21%) and psycho-oncologic care (- 12%), but also tumor surgery (- 9%). Substantial limitations were also reported for all other areas of multidisciplinary oncological care. CONCLUSIONS: This study documents the limitations of oncological care during the COVID-19 pandemic and highlights the need to develop strategies to avoid similar limitations in the future.

Kapazität der onkologischen Versorgung in deutschen onkologischen Spitzenzentren während der ersten 2 Jahre der COVID-19-Pandemie Oncologic care capacity in German Comprehensive Cancer Centers during the first 2 years of the COVID-19 pandemic

Hintergrund Eine zunehmende Zahl von internationalen Studien zeigt, dass die COVID-19-Pandemie schwerwiegende negative Auswirkungen auf die rechtzeitige Diagnose von Krebs und auf die Krebsbehandlung hat. Ziel der Arbeit Ziel der Arbeit war die quantitative und qualitative Auswertung der Kapazitäten deutscher onkologischer Spitzenzentren (Comprehensive Cancer Centers, CCCs) in verschiedenen Bereichen der komplexen onkologischen Versorgung im Zeitraum März 2020 bis Juni 2022. Material und Methoden Unter 18 CCCs in Deutschland erfolgte zwischen März 2020 und Juni 2022 eine prospektive regelmäßige Panelerhebung. Ergebnisse Die COVID-19-Pandemie hat in den ersten beiden Jahren das onkologische Versorgungssystem in Deutschland substanziell beeinträchtigt. Anhaltende Einschränkungen der Versorgung in den CCCs betrafen in erster Linie die Nachsorge (−21 %) und die Psychoonkologie (−12 %), aber auch Tumoroperationen (−9 %). Deutliche Funktions- und Kapazitätseinschränkungen fanden sich ebenso in allen weiteren Bereichen der multidisziplinären onkologischen Betreuung. Diskussion Die Studie dokumentiert die eingeschränkte onkologische Versorgung der Bevölkerung während der COVID-19-Pandemie. Die Auswirkungen lassen sich noch nicht vollumfänglich darstellen. Dennoch müssen (jetzt) Strategien zur Vermeidung solcher Einschränkungen entwickelt werden.

Kapazität der onkologischen Versorgung in deutschen onkologischen Spitzenzentren während der ersten 2 Jahre der COVID-19-Pandemie

Background: An increasing number of international studies demonstrate serious negative effects of the COVID-19 pandemic on the timely diagnosis of cancer and on cancer treatment. Objectives: This study aimed to quantitatively and qualitatively evaluate the capacities of German Comprehensive Cancer Centers (CCCs) in different areas of the complex oncological care structure from March 2020 to June 2022. Materials and methods: Prospective, regular panel survey were conducted among 18 CCCs in Germany between March 2020 and June 2022. Results: The COVID-19 pandemic substantially affected the oncologic care system in Germany during the first 2 years. Persistent limitations of care in CCCs primarily affected follow-up (−21%) and psychooncologic care (−12%), but also tumor surgery (−9%). Substantial limitations were also reported for all other areas of the multidisciplinary oncological care. Conclusions: This study documents the limited oncological care available during the COVID-19 pandemic. Its impact on patients’ outcomes cannot be fully revealed as yet. Nevertheless, strategies to avoid similar limitations in the future need to be developed (now).

IgG seroprevalence of COVID-19 among people living with HIV or at high risk of HIV in south-west Germany: A seroprevalence study.

OBJECTIVES: Seroprevalence studies of SARS-CoV-2 have shown that there is a high number of undiagnosed missing cases. Seroprevalence of SARS-CoV-2 in people living with HIV (PLWH) is lacking. Therefore, we conducted a prospective cross-sectional study to estimate the seroprevalence of SARS-CoV-2 among PLWH without known diagnosis of COVID-19 in the south-west of Germany. METHODS: Serological testing for SARS-CoV-2 immunoglobulin G (IgG) antibodies based on two assays was performed in PLWH who visited the outpatient HIV centre of two hospitals from April to June 2020. Additionally, patients had to answer questionnaires about possible COVID-19-related symptoms and predefined risk factors. Moreover, we tested 50 non-HIV-infected patients receiving post- or pre-exposure (PEP/PrEP) HIV prophylaxis. RESULTS: In all, 594 (488 male, 106 female) PLWH (median age 51 years) and 50 PEP/PrEP-users were included in the study. The estimated seroprevalence of the PLWH cohort was 1.85% (11/594), with 11 positive tested cases in the cohort. Among all patients, only five had COVID-19-related symptoms. One PCR-positive patient did not show any antibody response in repeatedly carried out tests. None of the patients was hospitalized due to COVID-19. Three PrEP users were tested positive. Three patients had been previously diagnosed with SARS-COV-2 infection before inclusion. The used questionnaire did not help to detect SARS-CoV-2 positive patients. CONCLUSIONS: Despite the limitation of being only a snapshot in time because of the ongoing pandemic, to our knowledge this is the largest study so far on seroprevalence of SARS-CoV-2 in PLWH in Germany. Our study suggests that the seroprevalence of SARS-CoV-2 in PLWH is comparable to those previously reported for parts of the general German population and that the questionnaire used here might not be the best tool to predict COVID-19 diagnosis.

Killer immunoglobulin-like receptor 2DS5 is associated with recovery from coronavirus disease 2019.

BACKGROUND: Despite numerous advances in the identification of risk factors for the development of severe coronavirus disease 2019 (COVID-19), factors that promote recovery from COVID-19 remain unknown. Natural killer (NK) cells provide innate immune defense against viral infections and are known to be activated during moderate and severe COVID-19. Killer immunoglobulin-like receptors (KIR) mediate NK cell cytotoxicity through recognition of an altered MHC-I expression on infected target cells. However, the influence of KIR genotype on outcome of patients with COVID-19 has not been investigated so far. We retrospectively analyzed the outcome associations of NK cell count and KIR genotype of patients with COVID-19 related severe ARDS treated on our tertiary intensive care unit (ICU) between February and June 2020 and validated our findings in an independent validation cohort of patients with moderate COVID-19 admitted to our tertiary medical center. RESULTS: Median age of all patients in the discovery cohort (n = 16) was 61 years (range 50-71 years). All patients received invasive mechanical ventilation; 11 patients (68%) required extracorporeal membrane oxygenation (ECMO). Patients who recovered from COVID-19 had significantly higher median NK cell counts during the whole observational period compared to patients who died (121 cells/µL, range 16-602 cells/µL vs 81 cells/µL, range 6-227 cells/µL, p-value = 0.01). KIR2DS5 positivity was significantly associated with shorter time to recovery (21.6 ± 2.8 days vs. 44.6 ± 2.2 days, p-value = 0.01). KIR2DS5 positivity was significantly associated with freedom from transfer to ICU (0% vs 9%, p-value = 0.04) in the validation cohort which consisted of 65 patients with moderate COVID-19. CONCLUSION: NK cells and KIR genotype might have an impact on recovery from COVID-19.

Increased B-cell activity with consumption of activated monocytes in severe COVID-19 patients.

The pathogenesis of autoimmune complications triggered by SARS-CoV2 has not been completely elucidated. Here, we performed an analysis of the cellular immune status, cell ratios, and monocyte populations of patients with COVID-19 treated in the intensive care unit (ICU) (cohort 1, N = 23) and normal care unit (NCU) (cohort 2, n = 10) compared with control groups: patients treated in ICU for noninfectious reasons (cohort 3, n = 30) and patients treated in NCU for infections other than COVID-19 (cohort 4, n = 21). Patients in cohort 1 presented significant differences in comparison with the other cohorts, including reduced frequencies of lymphocytes, reduced CD8+T-cell count, reduced percentage of activated and intermediate monocytes and an increased B/T8 cell ratio. Over time, patients in cohort 1 who died presented with lower counts of B, T, CD4+ T, CD8+ T-lymphocytes, NK cells, and activated monocytes. The B/T8 ratio was significantly lower in the group of survivors. In cohort 1, significantly higher levels of IgG1 and IgG3 were found, whereas cohort 3 presented higher levels of IgG3 compared to controls. Among many immune changes, an elevated B/T8-cell ratio and a reduced rate of activated monocytes were mainly observed in patients with severe COVID-19. Both parameters were associated with death in cohort 1.

Protection strategy against outbreak of COVID-19 at a tertiary hematology-oncology: strengths and pitfalls.

Due to the worldwide COVID-19 outbreak it is mandatory for health care workers to develop containment strategies. Recently published data showed, that cancer patients might have a higher risk for severe course of the disease. We therefore developed a strategy of screening and containment for SARS-CoV-2 for hospitalized cancer patients. Our approach includes a temporary isolation in a so-called floating zone and testing strategy for screening of asymptomatic individuals by pooling of samples before RT-PCR amplification. Patients as far as health care professionals got tested twice a week. Nurses and physicians entered the floating zone with full body protection. Within 8 weeks we tested 418 individuals (professionals and patients) in total. Only 2 patients had COVID-19 without documented further transmission of SARS-CoV-2. We therefore think that our strategy might be a useful approach to protect inpatients with cancer at high risk for SARS-CoV-2 infection during this ongoing pandemic.

Prolonged Course of COVID-19-Associated Pneumonia in a B-Cell Depleted Patient After Rituximab.

Patients with pre-existing comorbidities and immunosuppression are at greater risk for SARS-CoV-2 infection and severe manifestations of COVID-19. This also includes cancer patients, who are shown to have a poor prognosis after infection. Here, we describe the case of a 72-year old male patient with B-cell depletion after maintenance treatment with rituximab for non-Hodgkin-lymphoma who had a prolonged COVID-19 course and initial false negative test results. Our case highlights the diagnostic pitfalls in diagnosing COVID-19 in B-cell depleted patients and discuss the role of B-cell depletion in the course and treatment of COVID-19. Furthermore, we investigated peripheral blood monocytes and SARS-CoV-2 specific T cells in our patient. In conclusion, our case report can help physicians to avoid diagnostic pitfalls for COVID-19 in hemato-oncological patients under chemoimmunotherapy and tries to explain the role of B-cell depletion and SARS-CoV-2 specific T cells in this context.