Search

Summary: The use of CD19 chimeric antigen receptor T‐cell (CAR‐T) therapy for relapsed/refractory solid organ transplantation (SOT)‐related post‐transplant lymphoproliferative disorder (PTLD) is not well studied. We conducted a multicentre, retrospective analysis of adults with relapsed/refractory SOT‐associated PTLD. Among 22 relapsed/refractory SOT‐PTLD patients, the pathology was monomorphic B cell. Prior SOTs included 14 kidney (64%), three liver (14%), two heart (9%), one intestinal (5%), one lung (5%), and one pancreas after kidney transplant (5%). The median time from SOT to PTLD diagnosis was 107 months. Pre‐CAR‐T bridging therapy was used in 55% of patients, and immunosuppression was stopped completely before CAR‐T infusion in 64%. Eighteen (82%) patients experienced cytokine release syndrome: one (5%) each grade (G) 3 and G4. The immune effector cell‐associated neurotoxicity syndrome was observed in 16 (73%) patients: six (27%) G3 and two (9%) G4. The overall response rate was 64% (55% complete response). Three patients (14%) experienced allograft rejection after CAR‐T. The two‐year progression‐free survival and overall survival rates were 35% and 58%, respectively. Additionally, the achievement of CR post‐CAR‐T was strongly associated with survival. Collectively, the safety and efficacy of CD19 CAR‐T therapy in relapsed/refractory SOT‐related PTLD appeared similar to pivotal CAR‐T data, including approximately one‐third of patients achieving sustained remission. [ABSTRACT FROM AUTHOR]

The precise role of positron emission tomography (PET/CT) for predicting relapse/progression in multiple myeloma remains uncertain. We compared the predictive values of PET/CT, concurrent laboratory testing (labs), and their combination in prediction of 12-month progression, as determined by current International Myeloma Working Group (IMWG) criteria. PET/CT and labs (serum chemistry, β2-microglobulin, immunofixation, bone marrow biopsy, serum free light chains) were reviewed, and date of relapse/progression was determined by IMWG criteria. The median time from therapy to PET/CT imaging was 12.0 months (1.0-110) and median time to progression (TTP) was 29.8 months (1.6-130+). Overall survival and survival-without-progression at last follow-up were 84% and 49%, respectively. Sensitivity of PET/CT for predicting relapse/progression was lower than that of labs (0.67 vs. 0.89, ns), but PET/CT was more specific (0.89 vs. 0.79, ns). When labs and PET/CT data were combined, a positive result for either test was 89% sensitive and a positive result for both tests was 100% specific for predicting 12-month progression of disease. Kaplan-Meier analysis showed significantly greater TTP for those with a negative vs. positive PET/CT ( P = 0.0005), negative vs. positive labs ( P < 0.0001), and both tests negative vs. both tests positive ( P < 0.0001). Combining PET/CT with laboratory data improves the accuracy of prediction of relapse/progression within 12 months compared with each test alone. Thus, integration of PET/CT into myeloma follow-up is recommended, and the impact of this approach on management should be explored. [ABSTRACT FROM AUTHOR]

Summary. Malignant plasma cells generally grow within the bone marrow microenvironment; however, they can also grow at extramedullary sites. To identify the tumour-specific alterations required for extramedullary growth, we analysed the expression profiles of a series of plasma cell neoplasms including primary multiple myeloma (MM), plasma cell leukaemia (PCL) and extramedullary plasmacytoma (EPC). Hierarchical clustering analysis segregated the EPCs from the remaining samples, and revealed an expression pattern associated with angiogenesis in the EPCs, involving higher expression of the genes TIE2, NOTCH3 , CD31 and endoglin. Direct comparison of EPC samples with the MM samples identified 156 genes significantly upregulated and 85 genes significantly downregulated (P < 0·005, t -test) in the EPCs, including several genes involved in angiogenesis and adhesion that were upregulated (including angiopoietin 1, SPARC, Notch3 and fibronectin 1). Immunohistochemical staining demonstrated CD31 and endoglin protein expression in the EPC tumour cells, which are both angiogenesis related and could confer malignant plasma cells with the ability to grow outside the normal bone marrow environment. Defining how malignant plasma cell growth is regulated in the bone marrow versus at extramedullary sites will help to delineate the mechanisms underlying the dependence of tumour cell growth on angiogenesis and cell adhesion. [ABSTRACT FROM AUTHOR]