Summary 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.

Up‐to‐date information on coronavirus disease 2019 (COVID‐19) outcomes and risk factors in haematopoietic cell transplantation (HCT) recipients is required to inform on decisions about cancer treatment and COVID‐19 mitigation strategies. We performed a meta‐analysis to address this knowledge gap. All studies with at least five patients who reported COVID‐19‐related deaths in HCT recipients were included. The primary outcome was COVID‐19‐related death. Secondary outcomes were COVID‐19‐related mechanical ventilation (MV) and intensive care unit (ITU) admission. The cumulative COVID‐19‐related death rate among HCT recipients was 21% (95% confidence interval [CI] 18%–24%), while MV and ITU admission rates were 14% (95% CI 11%–17%) and 18% (95% CI 14%–22%), respectively. Subgroup analysis showed higher death rates in patients who developed COVID‐19 within 12 months of HCT (risk ratio [RR] 1.82, 95% CI 1.09–3.03), within 6 months of receiving immunosuppressant drugs (RR 2.11, 95% CI 1.38–3.20) or in the context of active graft‐versus‐host disease (RR 2.38, 95% CI 1.10–5.16). Our findings support the idea that HCT should remain an integral part of cancer treatment during the COVID‐19 pandemic but also highlight the need to prioritise preventative measures in those patients who are at increased risk of adverse COVID‐19 outcomes.

BackgroundBehçet’s Disease (BD) is an autoimmune disease mostly presenting with recurrent oral and genital aphthosis, and uveitis. Patients are rarely refractory to immunosuppressive treatments. Autologous hematopoietic stem cell transplantation (aHSCT) is a standard of care in other autoimmune diseases. Some patients with BD have been treated with aHSCT based on compassionate use.ObjectivesEvaluate the outcome of aHSCT in adult patients with BD treated in member centers of the European Society for Blood and Marrow Transplantation (EBMT).MethodsAdults who received aHSCT primarily for BD were identified retrospectively in the EBMT registry and/or in published literature. Data were extracted from either medical records of the patient or from publications.ResultsEight out of 9 cases reported to the registry and extracted data of 2 further patients from literature were analyzed. Four were female, median age at onset of BD was 24y (range 9-50). Median age at aHSCT was 32y (27-51). Patients had received median 4 (2-11) previous lines of therapy (89% corticosteroids, 50% methotrexate, anti-TNFα therapy or cyclophosphamide). All patients had active disease before mobilization. Conditioning regimen was heterogeneous. Median follow-up was 48 months (range 6-240). No treatment-related mortality was reported. This procedure induced complete remission (CR) in 80%, partial remission in 10% and lack of response in 10% of the patients. Relapse rate was 30% (2 relapses in patients in CR and 1 relapse in the patient in PR) with panuveitis (n=1), aphthosis (n=2) and arthralgia (n=1). Six patients were in CR. No late complications were reported.ConclusionaHSCT has an acceptable safety profile and represents a feasible and relatively effective procedure in severe and conventional treatment-resistant cases of BD and has the potential to stabilize BD in patients with life-threatening involvements.

CTLA-4 is a crucial immune checkpoint receptor involved in the maintenance of immune homeostasis, tolerance, and tumour control. Antibodies targeting CTLA-4 have been promising treatment for numerous cancers, but the mechanistic basis of their anti-tumoral immune boosting effects are poorly understood. Although the ctla4 gene also encodes an alternatively-spliced soluble variant (sCTLA-4), preclinical/clinical evaluation of anti-CTLA-4-based immunotherapies have not considered the contribution of this isoform. Here, we explore the functional properties of sCTLA-4 and evaluate the efficacy of isoform-specific anti-sCTLA-4 antibody targeting in murine cancer model. We show that expression of sCTLA-4 in tumour cells suppresses CD8+ T-cells in vitro, and accelerates growth and experimental metastasis of murine tumours in vivo. These effects were accompanied by modification of the immune infiltrate, notably restraining CD8+ T-cells in a non-effector state. sCTLA-4 blockade with isoform-specific antibody reversed this restraint, enhancing intratumoural CD8+ T-cell activation and cytolytic potential, correlating with therapeutic efficacy and tumour control. This previously unappreciated role of sCTLA-4 suggests that better understanding of the biology and function of multi-gene products of immune checkpoint receptors needs to be fully elucidated for improved cancer immunotherapy.