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.

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.

Vγ9Vδ2 T cells have a natural inclination to recognize malignant B cells in vitro via receptors for stress-induced self-ligands and TCR-dependent recognition of phosphoantigens (pAgs) generated in the mevalonate (Mev) pathway. This inclination is continuously challenged in vivo by the immune suppression operated by tumor cells. Multiple myeloma (MM) is a prototypic B-cell malignancy in which myeloma cells subvert the local microenvironment to reshape antitumor immune responses. In this study, we have investigated the immune competence of bone marrow (BM) Vγ9Vδ2 T cells in a large series of MM patients. We have found that the BM microenvironment significantly hampers the pAg-reactivity of BM Vγ9Vδ2 T cells, which become largely PD-1+ and are surrounded by PD-L1+ myeloma cells and increased numbers of PD-L1+ myeloid-derived suppressor cells (MDSC). Vγ9Vδ2 T-cell dysfunction is an early event that can be already detected in individuals with monoclonal gammopathy of undetermined significance (MGUS) and not fully reverted even when MM patients achieve clinical remission. Anti-PD-1 treatment increases the cytotoxic potential of Vγ9Vδ2 T cells by almost 5-fold after pAg stimulation, and appears to be a promising strategy for effective immune interventions in MM.

No abstract

No abstract

LTSs of CLL have an increased incidence of OC compared with the general population. CLL therapy is not a risk factor for OC in LTSs of CLL. The presence of an OC in these patients may be associated with shorter survival.

Chimeric antigen receptor-modified (CAR) T cells targeting CD19 have revolutionized the treatment of relapsed or refractory aggressive B-cell lymphomas, and their use has increased the cure rate for these cancers from 10 to 40%. Two second-generation anti-CD19 CAR T-cell products, axicabtagene ciloleucel and tisagenlecleucel, have been approved for use in patients, and the approval of a third product, lisocabtagene maraleucel, is expected in 2020. The commercial availability of the first two products has facilitated the development of real-world experience in treating relapsed or refractory aggressive B-cell lymphomas, shed light on anti-CD19 CAR T-cell products' feasibility in trial-ineligible patients, and raised the need for strategies to mitigate the adverse effects associated with anti-CD19 CAR T-cell therapy, such as cytokine release syndrome, neurotoxicity, and cytopenia. In addition, promising clinical data supporting the use of anti-CD19 CAR T-cell therapy in patients with indolent B-cell lymphomas or chronic lymphocytic leukemia have recently become available, breaking the paradigm that these conditions are not curable. Multiple clinical CAR T-cell therapy-based trials are ongoing. These include studies comparing CAR T-cell therapy to autologous stem cell transplantation or investigating their use at earlier stages of disease, novel combinations, and novel constructs. Here we provide a thorough review on the use of the anti-CD19 CAR T-cell products axicabtagene ciloleucel, tisagenlecleucel and lisocabtagene maraleucel in patients with indolent or aggressive B-cell lymphoma or with chronic lymphocytic leukemia, and present novel CAR T cell-based approaches currently under investigation in these disease settings.

No abstract