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Summary: Primary mediastinal (thymic) large B‐cell lymphoma (PMBCL) is an uncommon subtype of non‐Hodgkin lymphoma (NHL) that presents with a mediastinal mass and has unique clinicopathological features. Historically, patients with PMBCL were treated with R‐CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy ± involved field radiation. Since a phase II trial, published in April 2013, demonstrated excellent results using dose‐adjusted (DA) R‐EPOCH (rituximab, etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin), this treatment has gained popularity. We performed a retrospective, multicentre analysis of patients aged ≥18 years with PMBCL since January 2011. Patients were stratified by frontline regimen, R‐CHOP versus DA‐R‐EPOCH. 132 patients were identified from 11 contributing centres (56 R‐CHOP and 76 DA‐R‐EPOCH). The primary outcome was overall survival. Secondary outcomes included progression‐free survival, complete response (CR) rate, and rates of treatment‐related complications. Demographic characteristics were similar in both groups. DA‐R‐EPOCH use increased after April 2013 (79% vs. 45%, P < 0·001), and there was less radiation use after DA‐R‐EPOCH (13% vs. 59%, P < 0·001). While CR rates were higher with DA‐R‐EPOCH (84% vs. 70%, P = 0·046), these patients were more likely to experience treatment‐related toxicities. At 2 years, 89% of R‐CHOP patients and 91% of DA‐R‐EPOCH patients were alive. To our knowledge, this represents the largest series comparing outcomes of R‐CHOP to DA‐R‐EPOCH for PMBCL. [ABSTRACT FROM AUTHOR]

The hypomethylating agents ( HMAs) azacitidine and decitabine are both approved for treatment of myelodysplastic syndromes ( MDS) in the USA. In Europe, decitabine is not approved due to lack of survival advantage in randomized trials. The two drugs have not been compared in clinical trials. We identified patients diagnosed with MDS between 2004 and 2011 from the Surveillance, Epidemiology, and End Results ( SEER)-Medicare linked database in the USA who received ≥ 10 doses of either HMA. We estimated survival from HMA initiation with Kaplan-Meier methods and used multivariate Cox proportional hazards models to adjust for covariates. Analyses controlled for histological subtype and we conducted a subset analysis limited to patients with refractory anaemia with excess blasts ( RAEB). In 2025 HMA-treated patients, median survival was 15 months with no difference in survival based on the HMA received in adjusted analysis (decitabine versus azacitidine, hazard ratio = 1·06, 95% confidence interval: 0·94-1·19, P = 0·37). For RAEB patients ( n = 523), median survival was 12 months, with no significant difference based on HMA received. No significant survival difference was found between azacitidine and decitabine in patients with MDS, including RAEB. Importantly, population-based survival of azacitidine-treated RAEB patients was substantially shorter than in the AZA-001 clinical trial (11 versus 24·5 months). [ABSTRACT FROM AUTHOR]

A patient with relapsed and refractory chronic lymphocytic leukaemia with Richter transformation was treated with chimeric antigen receptor ( CAR)-modified T cells targeted for CD19 but later relapsed with a clonally related plasmablastic lymphoma. The loss of most routine markers of pre-plasma cell or B lymphoid differentiation (including CD19) highlights the ability of such mature lymphomas to evade lineage-specific targeted immunotherapy by differentiating along pathways comparable to their normal cellular counterparts. Molecular genetic evaluation demonstrated multiple independent lines of CD19-negative disease that eventually evolved in this single patient. Such plasticity represents potential challenges for antigen-directed CAR-T cell therapy, while serving as a testament to the selective pressure exerted by these engineered T cells over time. [ABSTRACT FROM AUTHOR]