BACKGROUNDThe prognosis of patients with early relapsed or refractory large B-cell lymphoma after the receipt of first-line chemoimmunotherapy is poor. METHODSIn this international, phase 3 trial, we randomly assigned, in a 1:1 ratio, patients with large B-cell lymphoma that was refractory to or had relapsed no more than 12 months after first-line chemoimmunotherapy to receive axicabtagene ciloleucel (axi-cel, an autologous anti-CD19 chimeric antigen receptor T-cell therapy) or standard care (two or three cycles of investigator-selected, protocol-defined chemoimmunotherapy, followed by high-dose chemotherapy with autologous stem-cell transplantation in patients with a response to the chemoimmunotherapy). The primary end point was event-free survival according to blinded central review. Key secondary end points were response and overall survival. Safety was also assessed. RESULTSA total of 180 patients were randomly assigned to receive axi-cel and 179 to receive standard care. The primary end-point analysis of event-free survival showed that axi-cel therapy was superior to standard care. At a median follow-up of 24.9 months, the median event-free survival was 8.3 months in the axi-cel group and 2.0 months in the standard-care group, and the 24-month event-free survival was 41% and 16%, respectively (hazard ratio for event or death, 0.40; 95% confidence interval, 0.31 to 0.51; P<0.001). A response occurred in 83% of the patients in the axi-cel group and in 50% of those in the standard-care group (with a complete response in 65% and 32%, respectively). In an interim analysis, the estimated overall survival at 2 years was 61% in the axi-cel group and 52% in the standardcare group. Adverse events of grade 3 or higher occurred in 91% of the patients who received axi-cel and in 83% of those who received standard care. Among patients who received axi-cel, grade 3 or higher cytokine release syndrome occurred in 6% and grade 3 or higher neurologic events in 21%. No deaths related to cytokine release syndrome or neurologic events occurred. CONCLUSIONSAxi-cel therapy led to significant improvements, as compared with standard care, in event-free survival and response, with the expected level of high-grade toxic effects. (Funded by Kite; ZUMA-7 ClinicalTrials.gov number, NCT03391466.

ScopeThis guideline is aimed at providing healthcare professionals with clear guidance on the management of patients with diffuse large B-cell lymphoma (DLBCL). Disease confined to specific extranodal sites, such as primary central nervous system lymphoma, testicular lymphoma, primary mediastinal large B-cell lymphoma, DLBCL of leg type, etc., is beyond the scope of this guideline. It is not the intention of this guideline to provide treatment recommendations for all situations and clinicians are advised to make management decisions taking into account individual patient circumstances. MethodologyThe guideline group was selected to be representative of UK experts in the assessment and treatment of DLBCL. Recommendations are based on a systematic review of published English language literature up to January 2015. MEDLINE database was searched using the key words DLBCL, treatment, radiotherapy and transplant. References from relevant publications were also searched. Other published guidelines, including the US National Comprehensive Cancer Network (NCCN) and European Society for Medical Oncology guidelines, were also noted.The writing group produced a draft guideline. Review of the manuscript was performed by the British Committee for Standards in Haematology (BCSH) by the Haemato-oncology sounding board of the British Society for Haematology (BSH). This consists of 50 or more members of the BSH who have reviewed this Guidance and commented on its content and applicability in the UK setting. It has also been reviewed by a patient representative nominated by the Lymphoma Association, but the Association does not necessarily approve or endorse the contents. Recommendation gradingThe Grading of Recommendations Assessment, Development and Evaluation (GRADE) nomenclature was used to evaluate levels of evidence and to assess the strength of recommendations. The GRADE criteria are specified on the BCSH web site. BackgroundThis is a new evidence-based guideline on behalf of the BCSH for the management of diffuse large B-cell non-Hodgkin lymphoma following a primary systematic review of the evidence by the writing group using the methodology described above.Diffuse large B-cell lymphoma is the most common non-Hodgkin lymphoma (NHL), accounting for 30-40% of all cases (Rodriguez-Abreu et al, 2007). Although most patients are cured with 6-8 cycles of R-CHOP (rituximab with cyclophosphamide, doxorubicin, vincristine and prednisolone) chemotherapy, about 10-15% have primary refractory disease and a further 20-30% relapse. The