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.

CAR-T and other adoptive cell therapies for B cell malignancies

B cell malignancies pose challenges due to therapeutic resistance and repeated relapse.Advances in adoptive cellular therapies including chimeric antigen receptor(CAR)-T cells have the potential to transform the treat-ment landscape in hematological and solid tumor cancers.Improvements in constructs of CAR-T have improved specificity in targeting malignant cells.Multiple clinical trials have demonstrated the efficacy of CAR-T and other cellular treatments.In spite of advances in cellular therapies,hurdles in managing toxicities and lingering resis-tance remain.This review aims to summarize current innovations in adoptive cellular therapies and introduces future paths of discovery that will enhance these therapies in the era of precision oncology.

Immunotherapeutic silk inverse opal particles for post-surgical tumor treatment

Recurrence of malignant tumor after surgical resection is the main reason of cancer treatment failure.Here,a novel kind of silk inverse opal particles(SIOPs)for post-surgical tumor treatment is presented,and it is derived from colloid crystal bead templates by negatively replicating.Because of their abundant uniform nanopores,interconnected nanochannels and excellent biocompatibility,SIOPs could not only carry great amount of anti-tumor drugs for tumor therapy,but also could provide support for cell adhesion,proliferation and differentiation as the 3 D spherical scaffolds which is beneficial to the tissue repair at resection sites.It is demonstrated that the antibody drugs could maintain their high biological activity without any influences during the preparation of SIOPs and these particles were able to enhance the therapeutic efficacy and promote tissue regeneration after surgical resection with their multifunctional features.These prominent properties indicate the great potentials of SIOPs as a promising strategy for efficient postoperative cancer therapy.

Ruxolitinib plus steroids for acute graft versus host disease:a multicenter,randomized,phase 3 trial

Newly diagnosed patients with high-risk acute graft-versus-host disease(aGVHD)often experience poor clinical outcomes and low complete remission rates.Ruxolitinib with corticosteroids showed promising efficacy in improving response and failure free survival in our phase I study.This study(ClinicalTrials.gov:NCT04061876)sought to evaluate the safety and effectiveness of combining ruxolitinib(RUX,5 mg/day)with corticosteroids(1 mg/kg/day methylprednisolone,RUX/steroids combined group)versus using methylprednisolone alone(2 mg/kg/day,steroids-only group).Newly diagnosed patients with intermediate-or high-risk aGVHD were included,with risk levels classified by either the Minnesota aGVHD Risk Score or biomarker assessment.Patients were randomized in a ratio of 1:1 into 2 groups:99 patients received RUX combined with methylprednisolone,while the other 99 received methylprednisolone alone as the initial treatment.The RUX/steroids group showed a significantly higher overall response rate(ORR)on day 28(92.9%)compared to the steroids-only group(70.7%,Odds Ratio[OR]=5.8;95%Confidence Interval[CI],2.4-14.0;P<0.001).Similarly,the ORR on day 56 was higher in the RUX/steroids group(85.9%vs.46.5%;OR=7.07;95%CI,3.36-15.75;P<0.001).Additionally,the 18-month failure-free survival was significantly better in the RUX/steroids group(57.2%)compared to the steroids-only group(33.3%;Hazard Ratio=0.46;95%CI,0.31-0.68;P<0.001).Adverse events(AEs)frequencies were comparable between both groups,with the exception of fewer grade 4 AEs in the RUX/steroids group(26.3%vs.50.5%P=0.005).To our knowledge,this study is the first prospective,randomized controlled trial to demonstrate that adding ruxolitinib to the standard methylprednisolone regimen provides an effective and safe first-line treatment for newly diagnosed high-risk acute GVHD.