Summary report written by Sophie van Lancker (TCWP) & Ida Bremer Ophorst, Marjola Gjerji, Maria Finch (PDWP), Ivan Moiseev (TCWP) & Marianna Maffeis (PDWP)
From 16 to 18 January 2025, in a sunny and pleasant Málaga, took place the combined EBMT Educational Meeting of the Transplant Complications (TCWP) and the Paediatric Diseases Working Parties (PDWP): Complications post CAR-T Cell Therapy in pediatric and adult patients.
NURSES EDUCATIONAL TRACK
This was the first time there was a combined congress with the two working party groups and with a separate nurses track within the congress.
We were glad to welcome 22 nurses from Spain, Italy, United Kingdom, France, the Netherlands, Belgium, Israel. The average attendance in the nurses’ track was 24. The meeting started the afternoon of the 16th ahead of the physicians educational program for its alignment of nursing-specific care points related to topics” for improved structure and clarity.
The first afternoon topics as the basics of CAR T and complications, apheresis, presentation of an adult and paediatric case about CRS and ICAN’s, and the perspective of a (P)ICU nurse were presented. The second part of the afternoon was delegated to the real life experience issues like the role of the bridging therapy, how to give information or communicate, the needs of the patient and family in psycho-social care. There was a good interaction in the group with a lot of questions asked, time to reflect on the topic and to share own experiences.
The second day was divided into sessions on the nurses track with sessions on the physician track. Nurses were kindly asked to join the sessions of the physicians when the topics as supportive care and monitoring, prophylaxis of cytokine release syndrome with the new approaches were presented and discussed. In the nurses track we continued also with new approaches like outpatient ambulatory care, the place of AI in CAR T treatment followed by a round table discussion about some of the ethical issues we experience as nurses in the taking care of the patient and the family. Two groups were formed. One group talked about the place of AI in the nursing care, the other group was focused on the complex considerations in healthcare, determining when “enough is enough”, balancing patient well-being, medical possibilities and ethical boundaries.
The last part of the nurses track intended to reflect on the care of CAR-T that is changing. In this session the presenters zoomed in on developments and new technologies and gives a change to work together to solve CAR-T problems. The session was closed with a practical escape room (escape box) presented a case from a potential CAR T patient that has to be resolved before opening the final box. The atmosphere of this meeting was very nice, cozy and an especially contributing meeting focusing on learning, sharing experiences between hospitals. Trying to give the whole picture of CAR T care and complications for nurses by the multidisciplinary approach of the speakers.
PHYSICIANS EDUCATIONAL TRACK
After the greetings of the EBMT organizers: Krzysztof Kałwak from Pediatric Disease working party, Zinaida Perić from Transplant Complications working party and the local organizer Alberto Mussetti, the first session started with the description of patient journey through CAR-T therapies. Loyre Bento presented a clinical case that immediately introduced the topic of CAR-T accessibility and availability followed by an interesting debate with the audience. Then Olaf Penack described the use of CAR-T in multiple myeloma. Giovanna Lucchini talked about the use of Tisagenlecleucel in pediatric patients, focusing of the important aspects of apheresis. She explained that patients with high peripheral disease burden (>10-20 x10E9/L) and sufficient circulating T cells (and absolute lymphocyte count of>500 cells/uL or a peripheral blood CD3 count of >150/uL) may be able to undergo leukapheresis for Tisagenlecleucel before starting therapy for relapse. She examined in depth the bridging therapy to CAR-T, underlying the importance of disease control rather than remission with the aim to reduce infections and toxicity. She also gave some recommendation about the use Inotuzumab as bridge. Andrea Palasciano presented an interesting clinical case of a pediatric patient.
The topic of the second session was prophylaxis of cytokine release syndrome. The first speaker was Jacopo Mariotti, who brought some data of lymphomas in adult patients. He showed that the role for CRS for disease response is controversial and published studied have some limitations (in particular for the use of different CART products). He presented then some results of the use of steroids for prophylaxis of CRS and withs anti IL6 drugs and anti IL1. He concluded that severe CRS is associated with a worse outcome due to increased side effects (such as ICANS) resulting in higher relapse mortality. CRS pre-emptive/prophylactic strategies are not associated with increased incidence of relapse and can be advantageous by reducing CRS severity, ICANS and NRM but more studies are necessary to identify better patient at high risk of complications.
Giovanna Lucchini showed data about pediatric prophylaxis of CRS: data from literature on prophylactic use of Tocilizumab/steroids revealed no difference in expansion or persistence of CAR T cells, she also presented other agents such as Anakinra and Defibrotide. The second session ended with Krzysztof Kalwak who underlined the points to be discussed, the selection of patients for prophylaxis: patients with ALL high disease burden, patients with numerous recovering “normal” B cells in peripheral blood, patients with lymphoma in NR and heavily pretreated patients. A very interesting panel of discussion about supporting care followed with interactive participation of Michelle Kenyon, Grzegorz Basak, Victor Noriega. The third session explored the topic of Cytokine release syndrome, grading and management with the description of the symptoms in children by Krzysztof Kałwak and in adults by Olaf Penack and the help of two clinical cases presented by M. Isabel Sotelo and Eurides Rosa. The discussion revealed that to reduce the risk of early toxicity is crucial to reduce MRD before the infusion of CAR-T cells. Some personal experiences suggested also a more “aggressive” approach during the early phase of CR/ICANS in order to have a better outcome by evaluating the use of Tocilizumab/Siltuximab, Dexamethasone/Methylpresnisolone pulse (q12h), Anakinra (q6h). Strategies to reduce CRS/ICANS reported in literature are fractional CAR- T cell dosing (3 days), early intervention during low grade CRS (steroids/Toci), concurrent BTK inhibition (Ibturinib+ CAR T cells), concurrent JAK inhibition (Itacitinib+ CAR T cells). Preemptive strategy included the prohylactic use of Tocilizumab given on day 2, prophylactic dexamethasone 10 mg on days 0,1 and 2, the prophylactic use of Anakinra given on days 0-7.
The last session of the second day was dedicated to neurologic complications of CAR-T cell therapies. The session was moderated by Roser Velasco and Jochen Büchner. The session was started by Christian Schultze-Florey who in the form of practical cases presented the tools to establish the diagnosis of ICANS, like immune effector cell-associated encephalopathy (ICE) score and Monreal scale, the workout necessary to screen for ICANS. An overview was made on the use of first line dexamethasone, second line anakinra and third line strategies, which include high-dose methylprednisone, cyclophosphamide. The importance of using high-dose anakinra ≥300 mg/day was highlighted. The second speaker in the session was a neurologist Roser Velasco, who presented the clinical, radiological and laboratory features of classical Parkinson’s syndrome, parkinsons-like movement disorder after anti-BCMA CAR-T, peripheral neuropathy after anti-CD19 CAR-Ts, autonomous neuropathy, PRES syndrome. Also part of the talk was dedicated to the cases of direct fludarabine-induced neurotoxicity and its difference from a classical ICANS and other immune complications of CAR-T in terms of timing, clinical and radiological manifestations.
The last day incorporated two sessions on infectious complications of CAR-T and rare CAR-T complications. The first one was chaired by Ivan Moiseev and Rafael de la Cámara. Ivan Moiseev presented an overview of current evidence on the incidence of infectious complications after CAR-T in different diseases and the factors of immune disfunction after CAR-T leading to the certain spectrum of infections. The current recommendations and target patient subgroups for antibacterial, antifungal, anti-PJP prophylactic therapies and vaccination were covered in the talk. Then Martina Pennisi talked about the existing algorithms in distinguishing CRS and sepsis, which is the major cause of infection- related mortality after CAR-T. Such approaches as IL-6, IL-1beta, IL-18 cytokine panel, serial procalcitonin and CRP measurement. Also Martina Pennisi presented a practical approach with an alternate escalation of immunosuppression and antibiotics in case of a persistent fever. The second session of the day on rare CAR-T complications was chaired by Ivan Moiseev and Charlotte Graham. The session was started by Giovanna Lucchini, who presented the latest recommendations of ASBMT on the diagnosis of a secondary hemophagocytic lymphohistiocytosis/macrophage activation syndrome (MAS) and a necessary link to a preceding CRS. In the second part of the talk Giovanna Lucchini presented several cases which highlighted poor response of MAS to IL-6 therapies and standard dose steroids. Novel approaches, like high-dose anakinra, emapalumab and ruxolitinib were described. Veit Buecklein continued with the data on persistent cytopenias after CAR-T therapies. He demonstrated that up to 70% of patients experience cytopenias, while in 15% they persist beyond several months. Veit Buecklein showed the utility of HEMATOX10 score in defining the risk of non-relapse mortality after CAR-T and showed the outcome of treatment of cytopenias after CAR-T with thrombopoietin receptor agonists and autologous graft boost. Charlotte Graham in the following talk focused on late complications, including few cases of secondary T-cell malignancies, and second cancers, as well as on long-term psychological problems in recipients of CAR-T therapies. The necessity of histological confirmation of secondary malignancies and testing for CAR-T transgene in reference laboratories was highlighted. Jowita Frączkiewicz finalized the session with a case presentation of ALL with a relapsing course and CAR-T administered in a presence of severe fungal infection with complications.
Zinaida Peric and Krzysztof Kałwak closed the meeting, admitting high interest to the topic, high number of attendees and valuable support of sponsors and EBMT event team.
We hope to see you all again at our educational meetings!