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Summary: CD19‐directed chimeric antigen receptor (CAR) T‐cell therapy is an important therapy for relapsed or refractory acute lymphoblastic leukaemia, but its use carries the risk of immune effector cell‐associated neurotoxicity syndrome (ICANS). In children, severe ICANS is almost universally reported in association with cytokine release syndrome and is reversible. We describe two cases of severe, intractable neurotoxicity following CAR T‐cell therapy in children with pre‐existing central nervous system (CNS) vulnerabilities. The cases were atypical in their delayed onset and independence from cytokine release syndrome and did not respond to standard therapies. [ABSTRACT FROM AUTHOR]

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]

Summary: Patients with acute myeloid leukaemia (AML) have a five‐year survival rate of 28·7%. Natural killer (NK)‐cell have anti‐leukaemic activity. Here, we report on a series of 13 patients with high‐risk R/R AML, treated with repeated infusions of double‐bright (CD56bright/CD16bright) expanded NK cells at an academic centre in Brazil. NK cells from HLA‐haploidentical donors were expanded using K562 feeder cells, modified to express membrane‐bound interleukin‐21. Patients received FLAG, after which cryopreserved NK cells were thawed and infused thrice weekly for six infusions in three dose cohorts (106–107 cells/kg/infusion). Primary objectives were safety and feasibility. Secondary endpoints included overall response (OR) and complete response (CR) rates at 28–30 days after the first infusion. Patients received a median of five prior lines of therapy, seven with intermediate or adverse cytogenetics, three with concurrent central nervous system (CNS) leukaemia, and one with concurrent CNS mycetoma. No dose‐limiting toxicities, infusion‐related fever, or cytokine release syndrome were observed. An OR of 78·6% and CR of 50·0% were observed, including responses in three patients with CNS disease and clearance of a CNS mycetoma. Multiple infusions of expanded, cryopreserved NK cells were safely administered after intensive chemotherapy in high‐risk patients with R/R AML and demonstrated encouraging outcomes. [ABSTRACT FROM AUTHOR]

Treatment of relapsed/refractory B-precursor acute lymphoblastic leukaemia (R/R B-ALL) in children remains a challenge, with only 30-50% of patients being salvaged by intensive chemotherapy and allogeneic haematopoietic stem cell transplantation (HSCT),1 with a dismal survival for those who relapse after HSCT.2 Results of immunotherapy with blinatumomab or autologous/allogeneic chimeric antigen receptor (CAR)-T cells hold out a promise of better outcomes3-6 and are now moving to the front-line of treatment protocols for selected high-risk patients (AALL1721/CASSIOPEIA, NCT03876769). The panel database included 230 patients with B-ALL, and for 138 patients (60%) the referring centre sought advice on curative treatment. The panel recommended antibody therapy for 47 patients (34%): blinatumomab for 34 patients, inotuzumab for eight, either blinatumomab or inotuzumab for five. [Extracted from the article]