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

ABSTRACT: 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 multicenter observational study evaluating bendamustine toxicity in real-world practice. Patients receiving at least 1 dose of bendamustine with/without rituximab (R) for iNHL were included. Demographics, lymphoma and treatment details, and grade 3 to 5 adverse events (AEs) were analyzed and correlated. In total, 323 patients were enrolled from 9 National Health Service hospitals. Most patients (96%) received bendamustine-R, and 46%, R maintenance. Overall, 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 for 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 preinduction performance status (PS), poor premaintenance PS, and abnormal preinduction total globulins and in those receiving growth factors. Use of antimicrobial prophylaxis was variable, and 3 of 10 opportunistic infections occurred despite prophylaxis. In this real-world analysis, bendamustine-related deaths and treatment discontinuation were similar to those of trial populations of younger, fitter patients. Poor PS, mantle cell histology, and maintenance R 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 for maintenance-treated patients.

Outcomes of older patients with primary central nervous system lymphoma treated in routine clinical practice in the UK: methotrexate dose intensity correlates with response and survival.

Data on older patients with primary central nervous system lymphoma (PCNSL) are scarce. Comorbidities and performance status frequently compromise outcomes in this group. Medical records for consecutive patients ≥65 years (n = 244) with PCNSL diagnosed 2012-2017 from 14 UK centres were retrospectively reviewed. Of these 192 patients received methotrexate (MTX)-based treatment. Patients were categorised based on clinician's treatment choice into 'palliative' (n = 52), 'less intensive: MTX ± rituximab ± alkylators' (n = 74) and 'intensive: MTX/cytarabine combinations' (n = 118) groups. Complete remission (CR) rate, two-year progression-free survival (PFS) and overall survival (OS) rates were 49%, 11% and 24% for the less intensive and 69%, 40% and 50% for the intensive groups. Treatment-related mortality (TRM) was 6·8% for MTX-treated patients. Median MTX cumulative dose was 8·8 g/m2 (range 1·5-21) over a median of three cycles. Higher relative dose intensity of MTX (MTX-RDI) was associated with improved PFS and OS in both groups adjusting for age, Eastern cooperative oncology group (ECOG) score and baseline parameters. Two-year PFS and OS for patients receiving four or more induction cycles followed by consolidation (n = 36) were 65% and 70% respectively. Older patients completing MTX-based induction and consolidation had clinical outcomes similar to those in younger cohorts. These retrospective data suggest that maximising MTX-RDI and delivering consolidation in a subgroup of older patients may improve clinical outcomes.

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.

BACKGROUND: 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. PATIENTS AND METHODS: 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. RESULTS: 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 (p < .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, p < .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 (p < .001 in both cases). CONCLUSIONS: 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.