ABSTRACT
Background: Philadelphia-negatie chronic myeloproliferatie neoplasms (MPN) typically incur high rates of thrombosis and infections and cytoreductie drugs may modulate such risks. Aims: The present analysis aims at assessing the seerity and outcomes of MPN facing coronairus disease 2019 (COVID-19). Hence, we aimed to assess the impact of immunosuppressie agents and comorbidity burden in COVID- 19 outcome. Methods: The EPICOVIDEHA registry is an online surey (www.clinicalsureys.net) that has collected since April 2020 until January 2022 5,445 cases of COVID-19 in indiiduals with baseline haematological malignancies (Salmanton-García et al, 2021 Hemasphere) The surey is promoted by the European Hematology Association - Infectious Diseases Working Party (EHA-IDWP) and has been approed centrally by the Institutional Reiew Board and Ethics Committee of Fondazione Policlinico Uniersitario A. Gemelli - IRCCS - Uniersità Cattolica del Sacro Cuore, Rome, Italy (Study ID: 3226). Results: Oerall, 308 patients (5.6%) with MPN were obsered for a median of 102 days (IQR: 21-223, range 22-97) after COVID-19 diagnosis. Median age at infection was 69 years (IQR: 58-77, range 22-97) and at least one comorbidity was reported from most of the indiiduals (62.6%, n = 193). A large portion of patients had a history of cardiopathy (n=109, 35.4%), diabetes (n=40, 15.9%), or chronic pulmonary disease (n=44, 14.3%). Myelofibrosis (MF) (n=140, 45.4%) was the most prealent baseline malignancy, with 18 MF patients (12.9%) reporting 3 or more comorbidities. Out of the whole cohort, 72 patients (42.8% of MF) receied immunosuppressige therapies including steroids, immunomodulatory drugs (IMiDs) or JAK-inhibitors. Hospitalization and consecutie admission to intensie care unit was required for 187 (60.7%) and 45 (24%) patients, respectiely. At multiariate logistic regression, Hospital admission was predicted by age >70 years (OR 2.809;95% CI 1.651-4.779), exposure to immunosuppressie therapies (OR 2.802;95% CI 1.5380-5.103) and comorbidity burden. During the study follow-up (median 101 days;range 21-222) 84 patients deceased after a median time of 14 days (IQR: 8-49, range 0-457) since COVID-19 diagnosis. The fatality rate (FR) decreased from 40.3% (50 out of 124) in the first two quarters of year 2020 to 15.8% (3 out of 19) in the first two quarters of year 2021 (p<0.05). Death was principally attributable to COVID-19 in 58 patients (69.0%) and contributable by COVID-19 in 15 (17.9%). FR was particularly high (54 out of 140, 38.6%) in MF patients and in patients receiing immunosuppressie agents (32 out of 86, 37%). Moreoer, FR increased from 13.0% in indiiduals with no comorbidity to 36.0% and 62.1% in those with >2 or >3 comorbidities, respectiely. More specifically, three comorbidities independently increased the FR: chronic cardiopathy (HR 1.653;95%CI 1.017-2.687), chronic pulmonary disease (HR 1.847;95% CI 1.097-3.109), and diabetes mellitus (HR 1.712;95% CI 1.006-2.914). A heay comorbidity burden, namely 3 or more comorbidities (HR 2.956;95% CI 1.403-6.227), adanced age, namely >70 years (HR .809;95% CI 1.651-4.779), myelofibrosis (HR 2.501;95% CI 1.384-4.519), and ICU admission (HR 2.669;95% CI 1.641-4.342) independently predicted FR. (MF) (n=140, 45.4%) was the most prealent baseline malignancy, with 18 MF patients (12.9%) reporting 3 or more comorbidities. Out of the whole cohort, 72 patients (42.8% of MF) receied immunosuppressige therapies including steroids, immunomodulatory drugs (IMiDs) or JAK-inhibitors. Hospitalization and consecutie admission to intensie care unit was required for 187 (60.7%) and 45 (24%) patients, respectiely. At multiariate logistic regression, Hospital admission was predicted by age >70 years (OR 2.809;95% CI 1.651-4.779), exposure to immunosuppressie therapies (OR 2.802;95% CI 1.5380-5.103) and comorbidity burden. During the study follow-up (median 101 days;range 21-222) 84 patients deceased after a median time of 14 days (IQR: 8-49, range 0-457) since COVID-19 diagnosis. The fatality rate (FR) dec eased from 40.3% (50 out of 124) in the first two quarters of year 2020 to 15.8% (3 out of 19) in the first two quarters of year 2021 (p<0.05). Death was principally attributable to COVID-19 in 58 patients (69.0%) and contributable by COVID-19 in 15 (17.9%). FR was particularly high (54 out of 140, 38.6%) in MF patients and in patients receiing immunosuppressie agents (32 out of 86, 37%). Moreoer, FR increased from 13.0% in indiiduals with no comorbidity to 36.0% and 62.1% in those with >2 or >3 comorbidities, respectiely. More specifically, three comorbidities independently increased the FR: chronic cardiopathy (HR 1.653;95%CI 1.017-2.687), chronic pulmonary disease (HR 1.847;95% CI 1.097-3.109), and diabetes mellitus (HR 1.712;95% CI 1.006-2.914). A heay comorbidity burden, namely 3 or more comorbidities (HR 2.956;95% CI 1.403-6.227), adanced age, namely >70 years (HR .809;95% CI 1.651-4.779), myelofibrosis (HR 2.501;95% CI 1.384-4.519), and ICU admission (HR 2.669;95% CI 1.641-4.342) independently predicted FR. Summary/Conclusion: COVID-19 infection led to a particularly dismal outcome in patients exposed to immunosuppressie agents and in those with chronic heart or pulmonary diseases, or diabetes. These data allow to tailor future strategies for preenting seere COVID-19 in MPN patients. (Table Presented).
ABSTRACT
Background: Patients with lymphoproliferatie diseases (LPD) appear particularly ulnerable to SARS-CoV-2 infection, partly because of the effects of the anti-neoplastic regimens (chemotherapy, signaling pathway inhibitors, and monoclonal antibodies) on the immune system. The real impact of COVID-19 on the life expectancy of patients with different subtypes of lymphoma and targeted treatment is still unknown. Aims: The aim of this study is to describe and analyse the outcome of COVID-19 patients with underlying LPD treated with targeted drugs such as monoclonal antibodies (obinutuzumab, ofatumumab, brentuximab, niolumab or pembrolizumab), BTK inhibitors (ibrutinib, acalabrutinib), PI3K inhibitors (idelalisib), BCL2 inhibitors (enetoclax) and IMIDs, (lenalidomide). Methods: The surey was supported by EPICOVIDEHA registry. Adult patients with baseline CLL or non-Hodgkin Lymphoma (NHL) treated with targeted drugs and laboratory-confirmed COVID-19 diagnosed between January 2020 and January 2022 were selected. Results: The study included 368 patients (CLL n=205, 55.7%;NHL n=163, 44.3%) treated with targeted drugs (Table 1). Median follow-up was 70.5 days (range 19-159). Most used targeted drugs were ITKs (51.1%), anti-CD20 other than rituximab (16%), BCL2 inhibitors (7.3%) and lenalidomide (7.9%). Of note, only 16.0% of the patients were accinated with 2 or more doses of accine at the onset of COVID-19. Pulmonary symptoms were present at diagnosis in 244 patients (66.2%). Seere COVID-19 was obsered in 47.8 % patients while 21.7% were admitted to to intensie care unit (ICU), being 55 (26.8%) CLL patients and 25 (15.3%) NHL patients. More comorbidities were reported in patients with seere-critical COVID-19 compared to those with mild- asymptomatic infection (p=0.002). This difference was releant in patients with chronic heart diseases (p=0.005). Oerall, 134 patients (36.4%) died. Primary cause of death was COVID-19 in 92 patients (68.7%), LPD in 14 patients (10.4%), and a combination of both in 28 patients (20.9%).Mortality was 24.2% (89/368) at day 30 and 34.5%(127/368) at day 200. After a Cox multiariable regression age >75 years (p<0.001, HR 1.030), actie malignancy (p=0.011, HR 1.574) and admission to ICU (p<0.00, HR 4.624) were obsered as risk factors. Surial in patients admitted to ICU was 33.7% (LLC 38.1%, NHL 24%). Mortality rate decreased depending on accination status, being 34.2% in not accinated patients, 15.9-18% with one or two doses, decreasing to 9.7% in patients with booster dose (p<0.001). There was no difference in OS in NLH s CLL patients (p=0.344), nor in ITKs s no ITKs treated patients (p=0.987). Additionally, mortality rate dropped from the first semester 2020 (41.3%) to last semester 2021 (25%). Summary/Conclusion: - Our results confirm that patients with B--mallignancies treatted with targeted drugs hae a high risk off seere infection (47.8%) and mortality (36.4%) from COVID-19. - Pressence of comorbidities,, especially heart disease,, is a risk factor for seere COVIID--19 infection in ourr series. - Age >75 years,, actie mallignancy att COVIID--19 onset and ICU admission were mortality risk factors. - COVIID--19 acination was a protectie factor for mortality,, een iin this popullation wiitth humorall immunity impairment. - The learning cure in the management of the infection throughout the pandemiic and the deelopmentt off COVIID--19 treatments showed benefit in this partticullarlly ullnerablle popullation? (Table Presented).
ABSTRACT
Background and study design: Patients with immunodeficiencies including CLL have an increased risk of severe infections and may not respond well to conventional vaccines. Two early international surveys reported that hospital-admitted Covid-19 patients with CLL had a high fatality rate (Mato et al., 2020;Scarfo et al., 2020). We recently showed that a robust and durable B and/or T cell immunity occurred in most convalescent CLL patients (Blixt et al., 2021). In contrast, the first publication on vaccination against SARS-CoV-2 in CLL reported seroconversion in only 39.5% of patients (Herishanu et al., 2021). We conducted a prospective clinical trial (COVAXID, clinicaltrials.gov: NCT04780659) in patients with various types of immunodeficiency and matched controls (n=539). Five equally sized cohorts were included: primary immunodeficiency, HIV, allogeneic transplantation or CAR-T, solid organ transplantation as well as CLL. The primary endpoint was seroconversion measured 2 weeks after the 2nd dose of the Pfizer-BioNTech vaccine (Comirnaty). Antispike antibodies in saliva (which may better correlate with protection, Khoury et al., 2020) and T cells (IFN-gamma ELISpot) were also measured. We report here the results of the CLL cohort. Results: Ninety CLL patients were included in four predefined subgroups: indolent untreated disease (n=30);prior chemoimmunotherapy including a CD20 mAb 9-30 months ago (n=20);ongoing BTKi therapy (n=30);and stopped/paused ibrutinib (all >3 months ago) (n=10). The median age was 70 years (range 23-87) and 67% were men. Median IgG was 6.7 g/L (range 1.0-20.8) and 50% had a value below the lower normal range. Reactogenicity occurred in 82.9 and 77.1% of the CLL patients and 81.6 and 85.0% of the controls after doses 1 and 2, respectively. The severity of reactogenicity was similar in patients and controls. AEs≥grade 2 was seen in five patients within 2 weeks after dose 2 but none was considered related to the vaccine. No hematological toxicity was observed. Data analysis on seroconversion is ongoing. Preliminary analysis of saliva showed that on D35 (i.e. 14 days after 2nd dose) 62% of CLL patients (95% of healthy controls) had developed IgG to S1S2 spike antigen compared to only 23% on D21 (i.e. 21 days after dose 1). Subgroup analysis (D35) indicates that ibrutinib-treated patients showed the lowest response in saliva whilst indolent and prior chemoimmunotherapy-treated groups were the best responders. A different pattern was observed for IFNgamma positive T cells with the highest responses in the (few) patients who had paused/stopped ibrutinib with other subgroups having lower T cell responses. Conclusions: This prospective clinical trial verified that the BNT162b2 mRNA vaccine was well-tolerated in patients with CLL. Our preliminary results indicate that anti-spike antibodies in saliva and T cell responses were frequently observed after full vaccination but with different response patterns in CLL subgroups. Details of the study including seroconversion and the overall response rate will be presented at the meeting.