Effects of the BTN162b2 mRNA COVID-19 vaccine in humoral and cellular immunity in patients with chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL), the most common leukemia in the western countries, is characterized by immunosuppression due to disease itself and cytotoxic treatments. Since the beginning of COVID-19 pandemic, patients with CLL appear to be a vulnerable population. In addition, phase III mRNA vaccine trials did not provide information about the efficacy in immunocomprised population. In CLL, the antibody-mediated response to SARS-CoV-2 vaccine is impaired. The goal of this study was to evaluate the effects of SARS-CoV-2 vaccination on humoral immune response and on cellular immunity in CLL patients. Humoral immune response to BNT162b2 messenger RNA COVID-19 vaccine was evaluated in 44 CLL patients comprising 20 treatment-naïve, 14 under treatment with ibrutinib and 10 in follow-up after completion of therapy. A positive serological response to SARS-CoV-2 vaccination with IgG titers higher than 13 UA/ml was detected in 54.6% of CLL patients with a higher response in patients who obtained remission after treatment. Reduced antibody response was detected in patients under ibrutinib treatment. T-cell response to overlapping pool of peptides representing the spike region was assessed in paired CLL samples collected before and after 1 month from the second dose of COVID-19 vaccine in treatment-naïve and ibrutinib-treated CLL patients using cytokine secretion assay. Both CD3+ CD4+ and CD3+ CD8+ T cells are able to mount a cellular response to spike peptides with secretion of IFNγ and TNFα before and after vaccination in both treatment naïve and ibrutinib-treated patients and this cellular immune response is independent by COVID-19 vaccination. Collectively, T cell response to spike peptides appeared more blunted in CLL patients under treatment with ibrutinib compared to untreated ones. Our study supports the need for optimization of vaccination strategy to achieve an adequate immune response keeping strict preventive measures by CLL patients against COVID-19.

High rate of durable responses with undetectable minimal residual disease with frontline venetoclax and rituximab in young and fit patients with chronic lymphocytic leukemia and an adverse biologic profile: results of the GIMEMA phase II LLC1518 - 'Veritas' study.

The GIMEMA phase II LLC1518 VERITAS trial investigated the efficacy and safety of frontline, fixed-duration venetoclax and rituximab (VenR) combination in young (≤65 years) and fit patients with chronic lymphocytic leukemia (CLL) and unmutated IGHV and/or TP53 disruption. Treatment consisted of the Ven ramp-up, six-monthly courses of the VenR combination, followed by six monthly courses of Ven single agent. A centralized assessment of measurable minimal residual disease (MRD) was performed on the peripheral blood (PB) and bone marrow (BM) by ASO-PCR at the end of treatment (EOT) and during the follow-up. The primary endpoint was the complete remission (CR) rate at the EOT. Seventy-five patients were enrolled; the median age was 54 years (range 38-65), 96% had unmutated IGHV, 9 (12%) had TP53 disruption, and 4% were IGHV mutated with TP53 disruption. The overall response rate (ORR) at the EOT was 94.7%, with a CR rate of 76%. An undetectable (u) MRD was recorded in 69.3% of patients in the PB and 58.7% in the BM. The 12-month MRD-free survival in the 52 patients with uMRD in the PB at the EOT was 73.1%. After a median follow-up of 20.8 months, no disease progressions were observed. Three patients have died, two due to Covid-19 and 1 to tumor lysis syndrome. The first report of the VERITAS study shows that frontline VenR was associated with a high rate of CRs and durable responses with uMRD in young patients with CLL and unfavorable genetic characteristics.

Facial and Oral Manifestations Following COVID-19 Vaccination: A Survey-Based Study and a First Perspective.

(1) Background: Severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) emerged in Wuhan, China, in late 2019. The development of effective and safe vaccines against SARS-CoV-2 has been extremely fast. The list of orofacial adverse effects of BNT162b2 and mRNA-1273 vaccines based on the clinical trials are reported to be rare. The aim of this study was to investigate the facial and oral manifestations of COVID-19 vaccination using a survey-based study. (2) Methods: The questionnaire was developed using Google Forms and sent anonymously to a total of 700 subjects (medical personnel) in Poland, Italy, and other EU countries. (3) Results: 223 people answered the questionnaire, mainly vaccinated with BNT162b2. Only 3.1% and 5.4% experienced oral and facial symptoms, respectively. General diseases presence and age have significant influence on the probability of oral symptoms occurrence after the second dose. Facial symptoms are correlated with general disease; autoimmune pathologies and age, at first and second dose, respectively. Gender, smoking and regular medication intake have significant influence on the probability of taking an absence day. Gender, age, and smoking have a significant influence on the duration of symptoms after second dose. (4) Conclusions: Based on the results of this preliminary survey, there is no observed significant correlation between vaccine administration for COVID-19 and facial and oral manifestations.

COVID-19 severity and mortality in patients with chronic lymphocytic leukemia: a joint study by ERIC, the European Research Initiative on CLL, and CLL Campus.

Chronic lymphocytic leukemia (CLL) is a disease of the elderly, characterized by immunodeficiency. Hence, patients with CLL might be considered more susceptible to severe complications from COVID-19. We undertook this retrospective international multicenter study to characterize the course of COVID-19 in patients with CLL and identify potential predictors of outcome. Of 190 patients with CLL and confirmed COVID-19 diagnosed between 28/03/2020 and 22/05/2020, 151 (79%) presented with severe COVID-19 (need of oxygen and/or intensive care admission). Severe COVID-19 was associated with more advanced age (≥65 years) (odds ratio 3.72 [95% CI 1.79-7.71]). Only 60 patients (39.7%) with severe COVID-19 were receiving or had recent (≤12 months) treatment for CLL at the time of COVID-19 versus 30/39 (76.9%) patients with mild disease. Hospitalization rate for severe COVID-19 was lower (p < 0.05) for patients on ibrutinib versus those on other regimens or off treatment. Of 151 patients with severe disease, 55 (36.4%) succumbed versus only 1/38 (2.6%) with mild disease; age and comorbidities did not impact on mortality. In CLL, (1) COVID-19 severity increases with age; (2) antileukemic treatment (particularly BTK inhibitors) appears to exert a protective effect; (3) age and comorbidities did not impact on mortality, alluding to a relevant role of CLL and immunodeficiency.