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.

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.

Non-Myelofibrosis Chronic Myeloproliferative Neoplasm Patients Show Better Seroconversion Rates after SARS-CoV-2 Vaccination Compared to Other Hematologic Diseases: A Multicentric Prospective Study of KroHem.

Disease- and treatment-mediated immunodeficiency might render SARS-CoV-2 vaccines less effective in patients with hematologic diseases. We performed a prospective non-interventional study to evaluate humoral response after one and two doses of mRNA-1273, BNT162b2, or ChAdOx1 nCoV-19 vaccine in 118 patients with different malignant or non-malignant hematologic diseases from three Croatian treatment centers. An electrochemiluminescent assay was used to measure total anti-SARS-CoV-2 S-RBD antibody titers. After one vaccine dose, 20/66 (33%) achieved seropositivity with a median antibody titer of 6.1 U/mL. The response rate (58/90, 64.4%) and median antibody titer (>250 U/mL) were higher after two doses. Seropositivity varied with diagnosis (overall p < 0.001), with the lowest rates in lymphoma (34.6%) and chronic lymphocytic leukemia (52.5%). The overall response rate in chronic myeloproliferative neoplasms (CMPN) was 81.3% but reached 100% in chronic myeloid leukemia and other non-myelofibrosis CMPN. At univariable analysis, age > 67 years, non-Hodgkin's lymphoma, active treatment, and anti-CD20 monoclonal antibody therapy increased the likelihood of no vaccine response, while hematopoietic stem cell recipients were more likely to respond. Age and anti-CD20 monoclonal antibody therapy remained associated with no response in a multivariable model. Patients with the hematologic disease have attenuated responses to SARS-CoV-2 vaccines, and significant variations in different disease subgroups warrant an individualized approach.