ABSTRACT
Chronic lymphocytic leukaemia (CLL) is associated with some degree of immune dysfunction as a result of the disease itself and/or treatment. COVID-19 has a major impact on patients with CLL who are at increased risk for severe disease and death. In this study, we aimed to understand the efficacy of anti-SARS-CoV-2 vaccines in patients with CLL. From January 2021, we collected data on 166 vaccinated patients with CLL followed at our site. Median age was 68 years (range 41-92);43 (26%) were treatment-naïve (TN), 25 (15%) were previously treated, 95 (57%) were on active therapy, and 3 (2%) were experiencing relapse. Most patients received BNT162b2 (87%), followed by mRNA-1273 (4%) and ChAdOx1-S (3%);data is missing in 6%. Serology testing was performed with the SARS-CoV-2 S1/S2 IgG assay (Elecsys® Anti-SARS-CoV-2) 2 to 3 weeks after second and third vaccine doses and considered negative for antibody titers below 0.4 U/ml. Vaccine response was evaluated post-dose 2 in 119 patients and post-dose 3 in 74 patients. Post second dose, a higher seroconversion rate was observed in TN patients and those with sustained clinical response after therapy discontinuation (42% and 46% respectively) compared with actively treated patients (20.5%;[p=0.024;p=0.048]). Antibody response rate in patients receiving BTKi was considerably lower 19.7% (12/61). Three (42.9%) out of 7 patients who received venetoclax monotherapy seroconverted. None of the patients exposed to anti-CD20 antibodies (3/8 with targeted therapy, 2/8 with chemotherapy, 3/8 as single agent) <12 months before vaccination responded. Among patients actively treated who failed to achieve a humoral response after two-dose, 25.6% responded to the third dose of vaccine, although with a weak antibody level (median 8.64 U/ml, range 0.55-175). Overall, post third dose a higher median (IQR) antibody titer (127.9 U/mL;0.55-2500) was observed compared to one post second dose (19.2 U/ml;0.86-2500) in patients on therapy. Notably, all patients in clinical remission after treatment present titers above the upper limit of quantification (>2500 U/mL) post third dose. Conclusions: Humoral immune response to the COVID-19 vaccine is impaired in most patients with CLL and correlates with treatment status.
ABSTRACT
BACKGROUND: Patients with chronic lymphocytic leukemia (CLL) may be more susceptible to COVID-19 related poor outcomes, including thrombosis and death, due to the advanced age, the presence of comorbidities, and the disease and treatment-related immune deficiency. The aim of this study was to assess the risk of thrombosis and bleeding in patients with CLL affected by severe COVID-19. METHODS: This is a retrospective multicenter study conducted by ERIC, the European Research Initiative on CLL, including patients from 79 centers across 22 countries. Data collection was conducted between April and May 2021. The COVID-19 diagnosis was confirmed by the real-time polymerase chain reaction (RT-PCR) assay for SARS-CoV-2 on nasal or pharyngeal swabs. Severe cases of COVID-19 were defined by hospitalization and the need of oxygen or admission into ICU. Development and type of thrombotic events, presence and severity of bleeding complications were reported during treatment for COVID-19. Bleeding events were classified using ISTH definition. STROBE recommendations were used in order to enhance reporting. RESULTS: A total of 793 patients from 79 centers were included in the study with 593 being hospitalized (74.8%). Among these, 511 were defined as having severe COVID: 162 were admitted to the ICU while 349 received oxygen supplementation outside the ICU. Most patients (90.5%) were receiving thromboprophylaxis. During COVID-19 treatment, 11.1% developed a thromboembolic event, while 5.0% experienced bleeding. Thrombosis developed in 21.6% of patients who were not receiving thromboprophylaxis, in contrast to 10.6% of patients who were on thromboprophylaxis. Bleeding episodes were more frequent in patients receiving intermediate/therapeutic versus prophylactic doses of low-molecular-weight heparin (LWMH) (8.1% vs. 3.8%, respectively) and in elderly. In multivariate analysis, peak D-dimer level and C-reactive protein to albumin ratio were poor prognostic factors for thrombosis occurrence (OR = 1.022, 95%CI 1.007â1.038 and OR = 1.025, 95%CI 1.001â1.051, respectively), while thromboprophylaxis use was protective (OR = 0.199, 95%CI 0.061â0.645). Age and LMWH intermediate/therapeutic dose administration were prognostic factors in multivariate model for bleeding (OR = 1.062, 95%CI 1.017-1.109 and OR = 2.438, 95%CI 1.023-5.813, respectively). CONCLUSIONS: Patients with CLL affected by severe COVID-19 are at a high risk of thrombosis if thromboprophylaxis is not used, but also at increased risk of bleeding under the LMWH intermediate/therapeutic dose administration.
Subject(s)
COVID-19 Drug Treatment , Leukemia, Lymphocytic, Chronic, B-Cell , Thrombosis , Venous Thromboembolism , Aged , Anticoagulants , COVID-19 Testing , Hemorrhage , Heparin, Low-Molecular-Weight , Humans , SARS-CoV-2ABSTRACT
Patients with chronic lymphocytic leukemia (CLL) may be more susceptible to Coronavirus disease 2019 (COVID-19) due to age, disease, and treatment-related immunosuppression. We aimed to assess risk factors of outcome and elucidate the impact of CLL-directed treatments on the course of COVID-19. We conducted a retrospective, international study, collectively including 941 patients with CLL and confirmed COVID-19. Data from the beginning of the pandemic until March 16, 2021, were collected from 91 centers. The risk factors of case fatality rate (CFR), disease severity, and overall survival (OS) were investigated. OS analysis was restricted to patients with severe COVID-19 (definition: hospitalization with need of oxygen or admission into an intensive care unit). CFR in patients with severe COVID-19 was 38.4%. OS was inferior for patients in all treatment categories compared to untreated (p < 0.001). Untreated patients had a lower risk of death (HR = 0.54, 95% CI:0.41-0.72). The risk of death was higher for older patients and those suffering from cardiac failure (HR = 1.03, 95% CI:1.02-1.04; HR = 1.79, 95% CI:1.04-3.07, respectively). Age, CLL-directed treatment, and cardiac failure were significant risk factors of OS. Untreated patients had a better chance of survival than those on treatment or recently treated.