Efficacy and Safety of Obinutuzumab-chemotherapy Combinations in Front-line Treatment of Follicular Non-Hodgkin Lymphoma During the COVID-19 Pandemic: A Study of KROHEM, the Croatian Cooperative Group for Hematologic Diseases

Abstract

Obinutuzumab (G) has become part of front-line treatment of follicular lymphoma (FL) based on results of a large randomized study. Data on patients treated outside of clinical trials are lacking. We have retrospectively investigated efficacy and safety of G-based immunochemotherapy regimens in 114 patients treated in a real-life setting during a period of 2 years, largely coinciding with the COVID-19 pandemic. The response rate was 93.8%; 18-months overall (OS) and progression-free survival (PFS) were 88% and 84%, respectively. Patients treated with G-cyclophosphamide, vincristine and glucocorticoid + doxorubicine (CHOP) had statistically significantly superior OS and PFS compared to patients treated with G-bendamustine (G-B) (P = 0.002 and P = 0.006, respectively) due to an increase in lethal infections, most notably COVID-19, in the latter group. A total of 12 patients died during follow-up; 9 of 61 treated with G-B, 1 of 49 treated with G-CHOP and 2 of 4 treated with G-cyclophosphamide, vincristine and glucocorticoid (CVP). SARS-CoV-2 infection was diagnosed in 20 (17.5%) patients. All of the 7 treated with G-CHOP recovered, while 4 of 12 treated with G-B died. Immunoglobulin levels and severity of neutropenia were similar between the groups. In multivariate analysis, G-B in comparison to G-CHOP was an independent prognostic factor (P = 0.044, hazard ratio = 9.81) after adjustment for age, sex and Follicular Lymphoma International Prognostic Index (FLIPI). Based on our experience G has excellent antilymphoma activity in patients receiving front-line treatment for FL in real-life setting, but during the COVID-19 pandemic, it should be preferentially combined with CHOP, at least in patients younger than 65.

Infections associated with bendamustine and anti-CD20 antibody in untreated follicular lymphoma: a real-world study

“…With regard to COVID-19 infection, lethal infections were reported in patients with FL treated by GB regimen. 7 , 8 There was no severe outbreak of COVID-19 infection in Oita Prefecture during the present observation period, and none of the present patients were infected with COVID-19 during this period. The present results suggest that in real-world practice, when bendamustine with anti-CD20 antibody is used for previously untreated FL, it is important to manage CMV infection as well as bacterial and fungal infections.…”

“…However, the incidence and outcomes of infections in real-world clinical practice among untreated FL patients receiving the bendamustine regimen remain unclear, as a limited number of reports are available. 7 , 8 We conducted a retrospective observational study to clarify infections in real-world clinical practice following chemotherapy consisting of bendamustine combined with an anti-CD20 antibody for previously untreated FL.…”