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
Introduction Coronavirus disease 2019 (COVID-19) is a life-threatening condition of high relevance for co-morbid patients, such as those with baseline hematological malignancies (HM). One year after the diagnosis of the first COVID-19 case, at the end of 2020, the first vaccines against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were administered to the population, starting with individuals at highest risk of infection. EPICOVIDEHA aims to describe the epidemiology, vaccination strategies and mortality rates from HM patients at risk. Methods We collected clinical and epidemiological data from patients with laboratory-based diagnosis of SARS-CoV-2 infection after partial or complete vaccination. The study was sponsored by the European Hematology Association - Infectious Diseases Working Party. Patients were registered in the EPICOVIDEHA online survey between January 1, 2021 and July 31, 2021 from Europe and United States. Data captured included underlying conditions prior to SARS-CoV-2, HM status and management prior to SARS-CoV-2, SARS-CoV-2 vaccination and infection details and mortality. The survey will continue until December 31, 2021. Results Overall, 40 patients have been so far registered, 24 male and 16 females, the vast majority of them aged over 50 years (N=38, 95%). Three quarters of patients were affected by lymphoproliferative malignancies (chronic lymphoid leukemia [CLL] N=14 and non-Hodgkin lymphoma [NHL] and multiple myeloma [MM] N=8, each), followed by myelodysplastic syndrome (MDS) (N=4), acute myeloid leukemia (AML) (N=2) and others (chronic myeloid leukemia [CML], acute lymphoid leukemia [ALL], polycythemia vera [PV] and aggressive mastocytosis one of each). Thirty-one patients (77.5%) were receiving active treatment for underlying HM at the time of SARS-CoV-2 infection, with 16 of them being on chemotherapy in the month prior to infection. All patients were vaccinated with a median time from vaccine to SARS-CoV-2 infection of 45.5 days (IRQ 19-67.5). Twenty-nine patients received a mRNA vaccine (BioNTech/Pfizer N=28, Moderna COVE N=1), whereas the remaining 11 an inactivated vaccine (Sinovac CoronaVac N=6) and vector-based vaccine (AstraZeneca Oxford N=5). Twenty-three patients were completely vaccinated, of which 22 (97.5%) patients were immunized (a minimum of 15 days following second dose). On the contrary, among 17 patients partially vaccinated, none was immunized. In 9 cases, viral genomes were analyzed (English variant N=7, South Africa variant N=1, Indian variant N=1). Overall, 25/40 patients presented with a severe/critical infection (62.5%), 13 of which (52%) were fully vaccinated and immunized, whereas only 15 (37.5%) were asymptomatic or mildly symptomatic. Twenty-seven (92.5%) patients were admitted to hospital, 5/27 (18.5%) to ICU, all requiring mechanical ventilation. After a follow-up of 30 day from SARS-CoV-2 infection, 8 patients died (20%), with 7/8 deaths (87.5%) attributable to SARS-CoV-2. There was no difference in overall survival between those patients that received 2 doses of vaccine or 1 dose (figure 1a), as well as no difference being observed between patients with and without lymphoproliferative malignancies (figure 1b), patients that receiving/not receiving active treatment in the last month (figure 1c), or the type of vaccine injected (figure 1d). Conclusions Our survey, involving over 150 Hematology Departments around the world, provides some preliminary insights. The majority of patients who do not respond to vaccination are patients with lymphoproliferative diseases, as can also be observed for other types of vaccination (e.g., flu-vaccination). Dramatically the mortality observed in all patients, although lower than that observed in the pre-vaccination period which in our experience was around 31%, still remains high (20%). Recruitment to this survey continues, and we hope that with larger numbers of cases, more definitive conclusions can be drawn to develop strategies to keep these complex patients safe. [Formula presented] Disclosures: Lop z-Garcia: Celgene: Other: Speaker Honoraria;Abbvie: Other: Speaker Honoraria, Advisor, Travel and accommodation grants;Janssen: Other: Speaker Honoraria, Advisor, Travel and accommodation grants, Research Funding;Roche: Other: Speaker Honoraria, Travel and accommodation grants;Novonordisk: Other: Speaker Honoraria;Fresenius: Other: Speaker Honoraria. Glenthoej: Novo Nordisk: Honoraria;Agios: Consultancy, Membership on an entity's Board of Directors or advisory committees;Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees;bluebird bio: Consultancy, Membership on an entity's Board of Directors or advisory committees;Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees;Alexion: Research Funding. Mikulska: Biotest: Speakers Bureau;Janssen: Speakers Bureau;MSD: Speakers Bureau;Gilead: Speakers Bureau;Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Busca: Gilead Sciences: Other: Lecture Honoraria;Merck: Other: Lecture Honoraria;Pfizer Pharmaceuticals: Other: Lecture Honoraria;Basilea: Other: Lecture Honoraria;Biotest: Other: Lecture Honoraria;Jazz Pharmaceuticals: Other: Lecture Honoraria;Takeda: Membership on an entity's Board of Directors or advisory committees. Corradini: KiowaKirin;Incyte;Daiichi Sankyo;Janssen;F. Hoffman-La Roche;Kite;Servier: Consultancy;AbbVie, ADC Theraputics, Amgen, Celgene, Daiichi Sankyo, Gilead/Kite, GSK, Incyte, Janssen, KyowaKirin, Nerviano Medical Science, Novartis, Roche, Sanofi, Takeda: Honoraria;AbbVie, ADC Theraputics, Amgen, Celgene, Daiichi Sankyo, Gilead/Kite, GSK, Incyte, Janssen, KyowaKirin, Nerviano Medical Science, Novartis, Roche, Sanofi, Takeda: Consultancy;Amgen;Takeda;AbbVie: Consultancy, Honoraria, Other: Travel and accommodations;Novartis;Gilead;Celgene: Consultancy, Other: Travel and accommodations;BMS: Other: Travel and accommodation;Sanofi: Consultancy, Honoraria;Incyte: Consultancy;Novartis, Janssen, Celgene, BMS, Takeda, Gilead/Kite, Amgen, AbbVie: Other: travel and accomodations. Hoenigl: Gilead, Pfizer, Astellas, Scynexis, and NIH: Research Funding. Klimko: Gilead Science, MSD, Pfizer: Membership on an entity's Board of Directors or advisory committees;Gilead Sciences, MSD, Pfizer Pharmaceuticals, and Astellas Pharma: Speakers Bureau. Pagliuca: Gentium/Jazz Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Gilead, Pfizer, and MSD: Research Funding. Passamonti: Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;AbbVie: Speakers Bureau;BMS: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau;Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Köhler: German Federal Ministry of Research and Education and the State of North Rhine-Westphalia, Germany: Other: Support;Miltenyi Biotec GmbH, Bergisch Gladbach, Germany, and the Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, Cologne, Germany: Other: Non-financial grants;Akademie für Infektionsmedizin e.V., Ambu GmbH, Astellas Pharma, European Confederation of Medical Mycology, Gilead Sciences, GPR Academy Ruesselsheim, MSD Sharp & Dohme GmbH, Noxxon N.V., and University Hospital, LMU Munich: Consultancy, Honoraria. Cornely: Amplyx, Basilea, BMBF, Cidara, DZIF, EU-DG RTD (101037867), F2G, Gilead, Matinas, MedPace, MSD, Mundipharma, Octapharma, Pfizer, Scynexis: Other: Grants or Contracts. Pagano: Gilead Science, MSD, Pfizer, Basilea, Janssen, Novartis, Jazz Pharmaceutical, Cidara: Membership on an entity's Board of Directors or advisory committees;Gilead Sciences, MSD, Pfizer Pharmaceuticals, Astellas Pharma: Speakers Bureau;Menarini: Consultancy.