Second versus first wave of covid-19 in patients with mpn

Introduction. MPN-COVID is a European LeukemiaNet cohort study, launched in March 2020 in patients with myeloproliferative neoplasms (MPN) with COVID-19. The first cohort of 175 cases was analyzed at the end of first wave (July 2020) and results provided estimates and risk factors of overall mortality (Barbui T. Leukemia, 2021), thrombosis incidence (Barbui T. Blood Cancer J, 2021), and post-COVID outcomes (Barbui T. Blood Cancer J, 2021). In the second wave of pandemic (June 2020 to June 2021), case-fatality risk in the general population has been found variable across different countries, and no information is available in MPN patients with COVID-19 diagnosed during the second wave in comparison with those of the first wave. Methods. In an electronic case report form, we registered a total of 479 cases of ET (n=161, 34%), PV (n=135, 28%), pre-PMF (n=49, 10%) and overt MF (n=134, 28%), from 39 European hematology units (Italy, Spain, Germany, France, UK, Poland, Croatia). Of these, 304 were diagnosed COVID-19 during the second wave. Results. Patients in the second wave were significantly different from those in the first wave, including parameters such as age (median: 63 vs. 71 years, p<.001), sex (females: 52% vs. 42%, p=0.037), MPN category (MF 24% vs. 34%, p=0.020), comorbidity (at least one comorbidity 63% vs. 74%, p=0.012), disposition (home: 68% vs. 23%, regular ward: 29% vs. 66%, ICU: 3% vs. 11%, p<.001), need of respiratory support (28% vs. 59%, p<.001) and degree of systemic inflammation (C-Reactive Protein: 51% vs. 74%, p=0.008;Neutrophil to Lymphocyte Ratio: 4.1 vs. 5.4, p=0.038). In regard to COVID-19-directed therapy, in the second wave steroids were more frequently prescribed (28% vs. 40%, p=0.007), while the use of antibiotics, antivirals, hydroxychloroquine and experimental therapies was significantly less frequent (p<.001 for all the differences). Interestingly, only 4 out of 46 patients (8.7%) discontinued Ruxolitinib during second-wave acute COVID (all MF admitted to regular ward). In the two waves, distribution probability of COVID-19 incidence by Kernel method showed a substantially similar shape, whereas the two incidence peaks were associated with very different mortality, as reported in Fig. 1A. The difference between the probability of death was highly significant during the first (n=175) vs. second (n=304): 31% vs. 9% at 60 days from COVID-19 diagnosis, respectively (p<.001) (Fig. 1B). Of note, among 26 deaths, 4 (15%) occurred at home, 19 (73%) on regular wards and 3 (12%) in the ICU, and death more frequently afflicted patients with (n=17, 65%) than ET (n=5, 19%) and PV (n=4. 15%) (p<.001). Independent risk factors for death in a multivariate Cox regression model fitted on the whole cohort and adjusted for the wave to which patients belonged, were age over 70 years (HR=5.2, 95% CI 1.8-15.1, p=0.002), male sex (HR=1.9, 95% CI 1.1-3.1, p=0.016), COVID-19 severity revealed by the need for respiratory support (HR=4.5, 95% CI 1.9-10.7, p=0.001), and Ruxolitinib discontinuation (HR=3.0, 95% CI 1.3-6.9, p=0.011). Conversely, in patients who continued this drug, no risk was documented (HR=1.21, p=0.566). Taking into account death as competing event, the second outcome of interest was the incidence of thrombosis, wich occurred in a significantly lower proportion of patients in the second wave compared to the first one (n=5 [1.6%] vs. n=14 [8.0%] at +60 days, respectively, SHR=0.20, p=0.002) (Fig. 1C). All the events, but one (n=4/5) were venous and were reported in patients with ET (SHR=4.4, 95% CI 1.8-10.7, p=0.001). Conclusions. This is the largest series of MPN patients who incurred COVID-19 from June 2020 onward, namely during the 'second COVID-19 wave'. Compared to the first wave, the second one recorded a lower overall COVID-19 severity, but Ruxolitinib discontinuation still remained a risk factor for a dismal outcome. Greater vulnerability of ET than PV in developing venous thrombosis was confirmed also during the second wave. This finding suggests that ET warrants a specific antithrombo ic prophylaxis in addition to heparin.

Managing hematological cancer patients during the COVID-19 pandemic: an ESMO-EHA Interdisciplinary Expert Consensus.

BACKGROUND: The COVID-19 pandemic has created enormous challenges for the clinical management of patients with hematological malignancies (HMs), raising questions about the optimal care of this patient group. METHODS: This consensus manuscript aims at discussing clinical evidence and providing expert advice on statements related to the management of HMs in the COVID-19 pandemic. For this purpose, an international consortium was established including a steering committee, which prepared six working packages addressing significant clinical questions from the COVID-19 diagnosis, treatment, and mitigation strategies to specific HMs management in the pandemic. During a virtual consensus meeting, including global experts and lead by the European Society for Medical Oncology and the European Hematology Association, statements were discussed and voted upon. When a consensus could not be reached, the panel revised statements to develop consensual clinical guidance. RESULTS AND CONCLUSION: The expert panel agreed on 33 statements, reflecting a consensus, which will guide clinical decision making for patients with hematological neoplasms during the COVID-19 pandemic.

A home care programme for the ramp-up and first courses of treatment with venetoclax and hypomethylating agents in the treatment of acute myeloid leukemia

Background: The combination of venetoclax (Ven) with hypomethylating agents (VenHMA) has shown promising results both in newly diagnosed and relapsed or refractory acute myeloid leukaemia (AML) patients, ineligible for intensive chemotherapy. Due to our expertise acquired in at-home management of diverse complex haematological procedures, we initiated in February 2020 an at-home (AH) programme for the VenHMA regimen. This AH-VenHMA programme included the initial dose ramp-up to prevent tumour lysis syndrome (TLS), a phase usually recommended to be performed as an inpatient hospital admission. Aims: Herein we present preliminary results of our AH experience during the first two cycles of VenHMA treatment for AML patients. Methods: Before implementation of AH-VenH programme, ramp-up was performed during a hospital admission (n=29, reference cohort). In Feb 2020, we initiated the VenH programme;outcome of in this patient cohort are compared with the reference cohort. In AH programme, prior to VenHMA initiation, medical evaluation is performed by a haematologist and a liaison nurse. Medical history, potential drug interactions and TLS risk are thoroughly evaluated. Laboratory tests (LT) including blood count and biochemistry are completed. Extensive health education is provided to patient and caregiver before the first cycle. A peripheral insertion intravenous catheter (PICC) is placed to all patients before starting ramp-up. Intravenous (IV) fluids by a portable pump (PP) are started 24hrs before the beginning of VenHMA, as well as uricosurics agents;patients are advised to maintain oral hydration. Daily morning visits during ramp-up are performed by trained nurses who complete vital sign, obtain LT, review therapeutic compliance, replaced PP and administer hypomethylating agent. Patients are started on Ven in an escalation schedule of 100mg on day 1, 200mg on day 2, and 400mg on day 3 of the cycle, they are advised to take Ven after dinner, following an explicit indication of our team given after daily LT review. An appropriate dose reduction is performed in patients receiving concomitantly CYP3A4 inhibitors. After achieving planned Ven full dose, IV fluids are ceased (Image 1). Patients are followed throughout the whole cycle by the AH team. Platelet transfusions are administered at-home while red cell concentrates are administered at the hospital, due to our transfusion policy. Results: Between February 2020 and January 2021, 22 AML patients (40 cycles) received VenHMA at-home. Fourteen patients were men (63.6%), with a median age of 73 years (23-83). Main characteristics were well balance in both patient cohorts. Neutropenia (86.3%), thrombocytopenia (90.9%) and anaemia (86.4%) were the most frequent adverse events (AEs). A trend to a lower proportion of febrile episodes was observed in the AH program (19/29 vs. 8/22, p=0.074). Hospital readmission rate after ramp-up was markedly low in the AH cohort, significantly lower than in the reference cohort (4/22 vs. 19/29, p = 0.001). TLS was not observed in any group. Main AEs are shown in table 1. Median days of at-home treatment were 49 (19-187). Discontinuation was due to refractoriness in 5 (22.7%) patients. Two patients presented SARS-CoV-2 infection in early March 2020, resulting in death in both cases. Summary/Conclusion: Home care during the ramp-up and early phase of VenHEM regimen is a feasible and safe option. An AH programme was followed by a low readmission rate and offers diverse benefits such as optimization of health resources and increase of the comfort and well-being of patients and their caregivers.