Guido Gini

Summary: Treatment options for relapsed/refractory (R/R) diffuse large B‐cell lymphoma (DLBCL) patients ineligible for autologous stem cell transplant (ASCT) or chimeric antigen receptor (CAR)‐T‐cell therapy remain limited. The PI3K inhibitor copanlisib has shown activity as a single agent in DLBCL. This phase II, single‐arm, multicentre trial evaluated copanlisib with rituximab and bendamustine (copa‐BR) in ASCT‐ and CAR‐T‐ineligible R/R DLBCL. Patients received six cycles of copa‐BR, followed by up to 12 cycles of copanlisib maintenance. The primary end‐point was 12‐month progression‐free survival (PFS). Thirty‐seven patients (aged 68–87 years, R/R after 1–2 prior lines) were enrolled. The overall response rate was 24.3%, with complete responses in 13.5%. After a median follow‐up of 20 months, the 12‐month PFS and overall survival rates were 25.1% and 44.5% respectively. Grade ≥3 toxicities included neutropenia (56.8%), infections (27.0%, including 6 death due to COVID‐19 infection with 25% fatality) and thrombocytopenia (16.2%). Due to limited efficacy, poor tolerability and emerging alternative treatments, the trial was terminated prematurely. Copa‐BR showed limited activity and an unfavourable safety profile, discouraging further investigation of this combination in ASCT‐ and CAR‐T‐ineligible R/R DLBCL.

Summary: Vaccinations are fundamental tools in preventing infectious diseases, especially in immunocompromised patients like those affected by non‐Hodgkin lymphomas (NHLs). The COVID‐19 pandemic made clinicians increasingly aware of the importance of vaccinations in preventing potential life‐threatening SARS‐CoV‐2‐related complications in NHL patients. However, several studies have confirmed a significant reduction in vaccine‐induced immune responses after anti‐CD20 monoclonal antibody treatment, thus underscoring the need for refined immunization strategies in NHL patients. In this review, we summarize the existing data about COVID‐19 and other vaccine's efficacy in patients with NHL and propose multidisciplinary team‐based recommendations for the management of vaccines in this specific group of patients.

Summary: Up to 10%–15% of diffuse large B‐cell lymphoma (DLBCL) are related to hepatitis C virus (HCV) infection, in particular in elderly patients. The Fondazione Italiana Linfomi has recently published a multicentre prospective observational study, the ‘Elderly Project’, on the outcome of DLBCL in patients aged ≥65 years, evaluated using a simplified comprehensive geriatric assessment. The aim of this study was to compare biological and clinical features of HCV positive (HCV+) with HCV negative (HCV−) cases. A total of 89 HCV+ patients were identified out of 1095 evaluated for HCV serology (8.1%). The HCV+ patients were older, less fit, and had frequent extranodal involvement. The cell‐of‐origin determination by Nanostring showed that HCV+ cases less frequently had an activated B‐cell profile compared to HCV− patients (18% vs. 43%). In all, 86% of HCV+ patients received rituximab‐cyclophosphamide, doxorubicin, vincristine (Oncovin) and prednisone (R‐CHOP)‐like immunochemotherapy. Grade 3–4 liver toxicity occurred in 3% of cases. Among centrally reviewed cases confirmed as DLBCL, the 3‐year overall survival of HCV+ patients was very similar to HCV− (63% vs. 61%, p = 0.926). In all, 20 HCV+ patients were treated with direct‐acting antiviral agents (DAAs), with good tolerance and sustained virological response in all cases. The 3‐year progression‐free survival for this subgroup was excellent (77%), suggesting DAAs' possible role in reducing the risk of relapse by eliminating the viral trigger.