Safety of bendamustine for the treatment of indolent non-Hodgkin lymphoma: a UK real-world experience

Introduction: Bendamustine is among the most effective chemotherapeutics for indolent B-cell non-Hodgkin lymphomas (iNHL), but trial reports of significant toxicity, including opportunistic infections and excess deaths, led to prescriber warnings. We conducted a multicentre observational study evaluating bendamustine toxicity in real-world practice. Methods: Patients receiving at least one dose of bendamustine (B) +/- rituximab (R) for iNHL were included. Demographics, lymphoma and treatment details and grade 3-5 adverse events (AEs) were analysed. Results: 323 patients were enrolled from 9 NHS hospitals. Most patients (96%) received BR and 46% R maintenance. 21.7% experienced serious AEs (SAE) related to treatment, including infections in 12%, with absolute risk highest during induction (63%), maintenance (20%), and follow-up (17%), and the relative risk highest during maintenance (54%), induction (34%) and follow-up (28%). Toxicity led to permanent treatment discontinuation in 13% of patients, and 2.8% died of bendamustine-related infections (n=5), myelodysplastic syndrome (n=3), and cardiac disease (n=1). More SAEs per patient were reported in patients with mantle cell lymphoma, poor pre-induction PS, poor pre-maintenance PS, abnormal pre-induction total globulins and in those receiving growth factors. Use of antimicrobial prophylaxis was variable, and 3/10 opportunistic infections occurred despite prophylaxis. Conclusion: In this real-world analysis, bendamustine-related deaths and treatment discontinuation were similar to trial populations of younger, fitter patients. Poor PS, mantle cell histology and maintenance rituximab were potential risk factors. Infections, including late onset events, were the most common treatment-related SAE and cause of death warranting extended antimicrobial prophylaxis and infectious surveillance, especially in maintenance-treated patients

Significance of baseline FDG-PET/CT scan as a method of staging regional lymph nodes in patients with operable distal oesophageal or gastroesophageal junction adenocarcinoma

<p><b>Background:</b> The new American Joint Committee on Cancer eighth edition (AJCC8) staging is the first to describe separate clinical and pathology staging systems, but still has low performance to predict prognosis in patients with oesophageal/gastroesophageal junction (O/GOJ) adenocarcinoma, who are candidates for surgery. Recent studies have demonstrated that O/GOJ cancer patients with 18F-fluorodeoxyglucose (FDG) avid regional lymph nodes (RLNs) may have poor prognosis. The aim of our study was to examine whether the baseline assessment of the FDG uptake of RLN improves the prognostic accuracy of the new AJCC8 staging.</p> <p><b>Patients and methods:</b> This single-centre retrospective study included patients with operable FDG avid O/GOJ adenocarcinoma treated with perioperative chemotherapy. All patients were reclassified according to the new AJCC8 clinical staging. Prognostic factors for time-to-progression (TTP) and overall survival (OS) were explored.</p> <p><b>Results:</b> Of 430 patients included in the study, 180 (41.9%) had FDG avid RLN at baseline PET/CT scan before starting perioperative chemotherapy. The presence of FDG avid RLN was significantly and independently associated with shorter TTP and OS, especially in clinical stage III patients (<i>p</i> < .001 in both cases). Stage III patients with FDG avid RLN had similar TTP and OS to those with stage IVA. Classifying stage III patients with FDG avid RLN into stage IVA led to a significant improvement of the prognostic accuracy of the new AJCC8 clinical staging system (Harrell’s concordance index improved from 0.555 to 0.588, <i>p</i> < .001). Of 430 patients starting perioperative chemotherapy, 332 underwent radical tumour resection. The presence of FDG avid RLN before starting perioperative chemotherapy could additionally predict a significantly shorter postoperative time-to-relapse and OS (<i>p</i> < .001 in both cases).</p> <p><b>Conclusions:</b> We propose that the incorporation of RLN status (by FDG PET/CT scan) into the AJCC8 staging system of O/GOJ adenocarcinoma improves its prognostic accuracy and may also improve treatment stratification.</p