Patients with Hematological Malignancies Treated with T-Cell or B-Cell Immunotherapy Remain at High Risk of Severe Forms of COVID-19 in the Omicron Era.

BACKGROUND: Patients with hematological malignancies are at greater risk of severe COVID-19 and have been prioritized for COVID-19 vaccination. A significant proportion of them have an impaired vaccine response, both due to the underlying disease and to the treatments. METHODS: We conducted a prospective observational study to identify the specific risks of the outpatient population with hematological diseases. RESULT: Between 22 December 2021 to 12 February 2022, we followed 338 patients of which 16.9% (n = 57) developed SARS-CoV-2 infection despite previous vaccination (94.7%). COVID-19 patients were more likely to have received immunotherapy (85.5% vs. 41%, p < 10-4), and particularly anti-CD20 monoclonal antibodies (40% vs. 14.9%, p < 10-4) and Bruton's tyrosine kinase inhibitors (BTKi) (7.3% vs. 0.7%, p < 10-2). There was no significant difference in demographic characteristics or hematological malignancies between COVID-19-positive and non-positive patients. Patients hospitalized for COVID-19 had more frequently received immunotherapy than patients with asymptomatic or benign forms (100% vs. 77.3%, p < 0.05). Hospitalized COVID-19 patients had a higher proportion of negative or weakly positive serologies than non-hospitalized patients (92.3% vs. 61%, p < 0.05). Patients who received tixagevimab/cilgavimab prophylaxis (n = 102) were less likely to be COVID-19-positive (4.9 vs. 22%, p < 0.05) without significant difference in hospitalization rates. CONCLUSION: In the immunocompromised population of patients with hematological malignancies, the underlying treatment of blood cancer by immunotherapy appears to be a risk factor for SARS-CoV-2 infection and for developing a severe form.

Prolonged in-hospital stay and higher mortality after Covid-19 among patients with non-Hodgkin lymphoma treated with B-cell depleting immunotherapy.

Prolonged Covid-19 is an emerging issue for patients with lymphoma or immune deficiency. We aimed to examine prolonged length of in-hospital stay (LOS) due to Covid-19 among patients with lymphoma and assess its determinants and outcomes. Adult patients with lymphoma admitted for Covid-19 to 16 French hospitals in March and April, 2020 were included. Length of in-hospital stay was analyzed as a competitor vs death. The study included 111 patients. The median age was 65 years (range, 19-92). Ninety-four patients (85%) had B-cell non-Hodgkin lymphoma. Within the 12 months prior to hospitalization for Covid-19, 79 patients (71%) were treated for their lymphoma. Among them, 63 (57%) received an anti-CD20 therapy. Fourteen patients (12%) had relapsed/refractory disease. The median LOS was 14 days (range, 1-235). After a median follow-up of 191 days (3-260), the 6-month overall survival was 69%. In multivariable analyses, recent administration of anti-CD20 therapy was associated with prolonged LOS (subdistribution hazard ratio 2.26, 95% confidence interval 1.42-3.6, p < 0.001) and higher risk of death (hazard ratio 2.17, 95% confidence interval 1.04-4.52, p = 0.039). An age ≥ 70 years and relapsed/refractory lymphoma were also associated with prolonged LOS and decreased overall survival. In conclusion, an age ≥ 70 years, a relapsed/refractory lymphoma and recent administration of anti-CD20 therapy are risk factors for prolonged LOS and death for lymphoma patients hospitalized for Covid-19. These findings may contribute to guide the management of lymphoma during the pandemic, support evaluating specific therapeutic approaches, and raise questions on the efficacy and timing of vaccination of this particular population.

Determinants of outcome in Covid-19 hospitalized patients with lymphoma: A retrospective multicentric cohort study.

BACKGROUND: Patients with lymphoma are immunocompromised because of the disease per se and its treatments. We aimed to describe the characteristics of patients with lymphoma hospitalized for Coronavirus Disease 2019 (Covid-19) and to analyze pre-Covid-19 determinants of mortality. METHODS: This retrospective multicentric cohort study used the Programme de Médicalisation des Systèmes d'Information database to identify all adult patients with lymphoma, hospitalized for Covid-19 in March and April 2020, in 12 hospitals of three French regions with pandemic outbreaks. The characteristics of lymphoma and Covid-19 were collected from medical charts. FINDINGS: Eighty-nine patients were included. The median age was 67 years (range, 19-92), 66% were male and 72% had a comorbidity. Most patients had B-cell non-Hodgkin lymphoma (86%) and had received a lymphoma treatment within one year (70%). With a median follow-up of 33 days from admission, 30-day overall survival was 71%, (95% confidence interval, 62-81%). In multivariable analysis, having an age ≥ 70 years (hazard ratio 2·87, 1·20-6·85, p = 0·02) and relapsed/refractory lymphoma (hazard ratio 2·54, 1·14-5·66, p = 0·02) were associated with mortality. Recent bendamustine treatment (n = 9) was also pejorative (hazard ratio 3·20, 1·33-7·72, p = 0·01), but was strongly associated with relapsed/refractory lymphoma. Remarkably, 30-day overall survival for patients < 70 years of age without relapsed/refractory lymphoma was 88% (78% - 99%). INTERPRETATION: Thirty-day mortality was associated with being older and relapsed/refractory lymphoma. Survival of patients younger than 70 years without relapsed/refractory lymphoma was comparable to that of the general population. FUNDING: There have been no specific funds to run this study.