2022 Chinese expert consensus and guidelines on clinical management of toxicity in anti-CD19 chimeric antigen receptor T-cell therapy for B-cell non-Hodgkin lymphoma

Adoptive cellular immunotherapy with chimeric antigen receptor(CAR)T cells has emerged as a novel modality for treating relapsed and/or refractory B-cell non-Hodgkin lymphoma(B-NHL).With increasing approval of CAR T-cell products and advances in CAR T cell therapy,CAR T cells are expected to be used in a growing number of cases.However,CAR T-cell-associated toxicities can be severe or even fatal,thus compromising the survival benefit from this therapy.Standardizing and studying the clinical management of these toxicities are imperative.In contrast to other hematological malignancies,such as acute lymphoblastic leukemia and multiple myeloma,anti-CD19 CAR T-cell-associated toxicities in B-NHL have several distinctive features,most notably local cytokine-release syndrome(CRS).However,previously published guidelines have provided few specific recommendations for the grading and management of toxicities associated with CAR T-cell treatment for B-NHL.Consequently,we developed this consensus for the prevention,recognition,and management of these toxicities,on the basis of published literature regarding the management of anti-CD19 CAR T-cell-associated toxicities and the clinical experience of multiple Chinese institutions.This consensus refines a grading system and classification of CRS in B-NHL and corresponding measures for CRS management,and delineates comprehensive principles and exploratory recommendations for managing anti-CD19 CAR T-cell-associated toxicities in addition to CRS.

Impact of genetic patterns on sorafenib efficacy in patients with FLT3-ITD acute myeloid leukemia undergoing allogeneic hematopoietic stem cell transplantation: a multi-center, cohort study

Sorafenib therapy improves overall survival(OS)in patients with FLT3 internal tandem duplication(ITD)acute myeloid leukemia(AML)undergoing allogeneic hematopoietic stem cell transplantation.We explored the efficacy of sorafenib therapy in this population with different concomitant genetic patterns.In this multi-center,cohort study,we enrolled patients with FLT3-ITD AML undergoing allogenic hematopoietic cell transplantation.Patients with sorafenib maintenance post-transplantation for at least four weeks were allocated to the sorafenib group,and otherwise to the control group.

Design,synthesis,and biological evaluation of Bcr-Abl PROTACs to overcome T315I mutation

Bcr-Abl threonine 315 to isoleucine 315(T315 I)gatekeeper mutation induced drug resistance remains an unmet clinical challenge for the treatment of chronic myeloid leukemia(CML).Chemical degradation of Bcr-AblT315 Iprotein has become a potential strategy to overcome drug resistance.Herein,we first described the design,synthesis,and evaluation of a new class of selective Bcr-AblT315 I proteolysis-targeting chimeric(PROTAC)degraders based on GZD824(reported as Bcr-AblT315 Iinhibitor by our group).One of the degrader 7 o with 6-member carbon chain linkage with pomalidomide exhibits the most potent degradation efficacy with DR of 69.89%and 94.23%at 100 and 300 nmol/L,respectively,and has an IC50 value of 26.8±9.7 nmol/L against Ba/F3T315 Icells.Further,7 o also displays substantial tumor regression against Ba/F3-Bcr-AblT315 Ixenograft model in vivo.