RESUMEN
The use of chimeric antigen receptor T cells (CAR-T) has increased since their approval in the treatment of several relapsed/refractory B cell malignancies. The management of their specific toxicities, such as cytokine release syndrome (CRS), tends to be better understood and well-defined. During the twelfth edition of practice harmonization workshops of the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC), a working group focused its work on the management of patients developing CRS following CAR-T cell therapy. A special chapter has been allocated to macrophage activation syndrome (MAS), a rare but life-threatening complication post-CAR-T. In addition to symptomatic measures and preemptive broad-spectrum antibiotics, immunomodulators such as tocilizumab and corticosteroids remain the corner stone for the treatment of CRS. Tocilizumab/corticosteroids-resistant CRS associated with haemophagocytosis markers (spleen and liver enlargement, hyperferritinaemia>10,000ng/mL, hypofibrinogenemia ) should direct the diagnosis towards an overlapping CRS/MAS. An adapted treatment will be based on high-dose IV anakinra and corticosteroids and chemotherapy with etoposide at late refractory stages. These complications and others delignate the need of close collaboration with an intensive care unit.
Asunto(s)
Síndrome de Activación Macrofágica , Receptores Quiméricos de Antígenos , Humanos , Receptores Quiméricos de Antígenos/uso terapéutico , Síndrome de Liberación de Citoquinas/terapia , Síndrome de Liberación de Citoquinas/tratamiento farmacológico , Síndrome de Activación Macrofágica/terapia , Síndrome de Activación Macrofágica/complicaciones , Recurrencia Local de Neoplasia/tratamiento farmacológico , Inmunoterapia Adoptiva/efectos adversos , Corticoesteroides/uso terapéutico , Tratamiento Basado en Trasplante de Células y TejidosRESUMEN
The immune effector cell-associated syndrome (ICANS) has been described as the second most frequent specific complication following CAR-T cell therapy. The median time to the onset of neurological symptoms is five days after CAR-T infusion. ICANS can be concomitant to cytokine release syndrome but often follows the resolution of the latter. However, 10 % of patients experience delayed onset after 3 weeks of CAR-T cell infusion. The duration of symptoms is usually short, around five days if an early appropriate treatment is given. Symptoms are heterogeneous, ranging from mild symptoms quickly reversible (alterations of consciousness, deterioration in handwriting) to more serious forms with seizures or even a coma. The ICANS severity is currently based on the ASTCT score. The diagnosis of ICANS is clinical but EEG, MRI and lumbar punction can help ruling out alternative diagnoses. The first line treatment consists of high-dose corticosteroids. During the twelfth edition of practice harmonization workshops of the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC), a working group focused its work on updating the SFGM-TC recommendations on the management of ICANS. In this review we discuss the management of ICANS and other neurological toxicities in patients undergoing of CAR-T cell therapy. These recommendations apply to commercial CAR-T cells, in order to guide strategies for the management neurological complications associated with this new therapeutic approach.
Asunto(s)
Receptores Quiméricos de Antígenos , Humanos , Receptores Quiméricos de Antígenos/uso terapéutico , Inmunoterapia Adoptiva/efectos adversos , Trasplante de Médula Ósea , Síndrome de Liberación de Citoquinas/etiologíaRESUMEN
CAR-T cells are an innovative treatment for an increasing number of patients, particularly since the extension of their indication to mantle lymphoma and multiple myeloma. Several complications of CAR T-cell therapy, that were first described as exceptional, have now been reported in series of patients, since its first clinical use in 2011. Among them, cardiac complications, delayed cytopenias, acute and chronic Graft versus Host Disease, and tumoral lysis syndrome are recognized as specific potent complications following CAR T-cells infusion. During the twelfth edition of practice harmonization workshops of the Francophone society of bone marrow transplantation and cellular therapy (SFGM-TC), a working group focused its work on the management of these complications with focuses the epidemiology, the physiopathology and the risk factors of these 4 side effects. Our recommendations apply to commercial CAR-T cells, in order to guide strategies for the management of complications associated with this new therapeutic approach.
Asunto(s)
Enfermedad Injerto contra Huésped/etiología , Cardiopatías/etiología , Inmunoterapia Adoptiva/efectos adversos , Neutropenia/etiología , Síndrome de Lisis Tumoral/etiología , Enfermedad Injerto contra Huésped/epidemiología , Humanos , Incidencia , Neutropenia/terapia , Receptores Quiméricos de Antígenos , Factores de Riesgo , Linfocitos T/trasplanteRESUMEN
Infections occurring after CAR T-cells are a common complication. At the acute phase of treatment following CAR T-cell infusion, the exact incidence of infections is unknown given the overlapping symptoms with cytokine release syndrome. The risk factors for infection include the malignant underlying disease and its multiple treatments, and an immunosuppressive state induced by CAR-T cells themselves and the treatment of their complications. During the twelfth edition of practice harmonization workshops of the Francophone society of bone marrow transplantation and cellular therapy (SFGM-TC), a working group focused its work on the management of post-CAR infectious complications. In this review we discuss anti-infection prophylaxis and vaccination of patients undergoing CAR T-cell therapy as well as a special chapter for the specific case of COVID-19. These recommendations apply to commercial CAR-T cells, in order to guide strategies for the management and prevention of infectious complications associated with this new therapeutic approach.
Asunto(s)
Infecciones Bacterianas/prevención & control , Inmunoterapia Adoptiva , Micosis/prevención & control , Receptores Quiméricos de Antígenos/uso terapéutico , Virosis/prevención & control , Trasplante de Médula Ósea , COVID-19/prevención & control , Trasplante de Células , Síndrome de Liberación de Citoquinas , Humanos , Inmunización , Huésped Inmunocomprometido , Inmunoglobulinas/uso terapéutico , Inmunoterapia Adoptiva/efectos adversos , Neoplasias/complicaciones , Neoplasias/terapia , Pneumocystis , Factores de RiesgoRESUMEN
In Europe, two CAR T-cell products, tisagenlecleucel (Kymriah™) and axicabtagene ciloleucel (Yescarta™), were approved in 2018. While these treatments are available for use, allogeneic hematopoietic stem cell transplantation centers still need to set up a dedicated care process inspired by established procedures in the field. In order to determine necessary resources and actors, each step of the CAR T-cell care process must be planned in advance. This process, implemented by the center's coordinating nurse, should be able to be adapted to each center's needs. The purpose of this workshop is to provide the organizational basis for such a process so that each center wishing to set up CAR-T cell activity can do so effectively. After detailing the coordinating nurse's role, we explain each step of the care process and specify essential additional tests.
Asunto(s)
Inmunoterapia Adoptiva/métodos , Antígenos CD19/uso terapéutico , Productos Biológicos , Congresos como Asunto/organización & administración , Trasplante de Células Madre Hematopoyéticas , Hospitalización , Humanos , Leucaféresis , Receptores de Antígenos de Linfocitos T/uso terapéutico , Sociedades MédicasRESUMEN
In an attempt to harmonize clinical practices among French hematopoietic stem cell transplantation centers, the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC) held its seventh annual workshop series in September 2016 in Lille. This event brought together practitioners from across the country. Our workshop discusses the creation of a patient care logbook for patients undergoing autologous hematopoietic cell transplantation.