Maria-Luisa Schubert, Anita Schmitt, Angela Hueckelhoven-Krauss, et al.
Conclusions: HD-CAR-1 is the first academic CAR T cell trial in Germany with in-house leukapheresis, CART manufacturing and administration. CART production was feasible for all enrolled patients so far. Patients responded clinically to treatment despite low numbers of administered CARTs. CARTs displayed a highly favorable safety profile, migrated into different compartments and were partly detectable for more than 3 months following administration. HD-CAR-1 accounts for clinical evaluation of third-generation CARTs that might contribute to long-term CART persistence, hence improving responses in treated patients.
Boris Fehse, Anita Badbaran, Carolina Berger, et al.
Conclusions: We have established a novel dPCR assay for sensitive detection of Axi-cel CAR-T cells in vivo. Our assay is excellently suited as a diagnostic tool to monitor the infused cells in real-time in different body fluids.
Adrián Fernández, Lucía Fernández, Isabel Mirones et al.
Conclusions: NKG2D CAR memory T cells are essentially safe. Only supraphysiological levels of sNKG2DL caused NKG2D-CAR downmodulation, while normal levels induce cell proliferation and production of pro-inflammatory cytokines. Altogether these data suggest NKG2D CAR could be more resistant to the negative effects of sNKG2DL than endogenous NKG2D receptor. However, we did not observe a beneficial clinical effect in this advance situation.
Francis Ayuk, Boris Fehse, Dietlinde Janson, et al.
Conclusions: In conclusion, we for the first time present data on proliferation and persistence of allogeneic donor-derived 4-1BB based CAR-T cells under therapeutic levels of cyclosporine A. This indicates that for patients with early relapse after allo-HSCT with ongoing immunosuppression donor CAR-T cell therapy may be a feasible Treatment.
Emilie Robert, Claire Fontenille, Plotine Crochet, et al.
Conclusions: With the creation of the first biobank focused on CAR-T cells treated patients, the CALYM-CRYOSTEM collaboration opens new research perspectives by providing access to raw material. This approach would impact CAR-T cells treatments by providing a large amount of post-infusion data, contributing to consolidating knowledge on this recent cell-based therapeutic approach.
This initiative, focused on lymphoma, sets up the bases of the constitution of new type of collection integrating complementary expertise and actors in CAR-T care and research. It will constitute a proof of concept for other initiatives in this field, independently of the initial hematological disease.
Giovanna Del Principe, Giovanna Leone, Annalisa Ruggeri, et al.
Conclusions: Sufficient numbers of cells can be obtained from pediatric patients with BW < 15 kg, with a median value of processed TBV of 2.7L (1.6-4.3), provided that their lymphocyte counts are >900/ul. All patients reached the target cells in a single apheresis, including 2 patients with lympho-CE < 30%. In 56/70 (80%) of collections, lympho-CE was =50%.
Density gradient purification with the Sepax device is helpful to remove a fraction of RBC, allowing subsequent cryopreservation of pure products in which CD3+ cell concentration is higher with respect to other cellular components.
Silvia Monsalvo, Gonzalo Balsera, Gillen Oarbeascoa, et al.
Conclusions: In most patients undergoing CART cell therapy, leukapheresis is well-tolerated and adequate numbers of CD3+ lymphocytes are collected. A personalized approach to the collection process is the essential first step for CART cell immunotherapy. However, further studies of larger cohorts of patients including new variables are necessary to confirm this findings to ensure that all patients can have sufficient cells for manufacturing.
Fang Ni, Yongxian Hu, Alex Hong Chang, He Huang (China)
our results showed that CAR-T cell treatment could be safely administered in patients with Concomitant Hepatitis B Virus infection. Considering the small group sample size and retrospectively analysis, the risk of HBV reactivation with prophylactic entecavir treatment after CAR-T cell treatment should be further evaluated in large and prospective studies.
Madiha Iqbal, Sangeetha Gandhi, Abdullah Alselah, et al.
Conclusions: Our analysis did not identify rituximab or any other patient- or pre-CAR-treatment related factors to be associated with persistence of leukopenia and thrombocytopenia at day +90 post axi-cel.
Christian R Schultze-Florey, Victoria Panagiota, Ivan Odak, et al.
Conclusions: Immune cell monitoring of lymphocyte subsets in CAR T cell patients may provide important insights in immune function supporting CAR T cell activity. In this prospective single center pilot study we describe an altered lymphocyte subset phenotype in patients failing to respond to Tisagenlecleucel. The phenotype consisted of a reduced CD4:CD8 ratio, lower CD3-CD56+ frequencies and central memory populations together with higher CD8+ and CD3+CD56+ populations. However, these data are limited by the small cohort size and warrant further validation in a larger cohort.
Katie Ahern, Shafqat Inam, Katie Walker, et al.
Conclusions: CAR T-cell therapy appears to have a less significant impact on nutritional status than other similar treatments for haematological malignancies, primarily due to a lower incidence in adverse effects. However, all patients undergoing treatment should be nutritionally screened prior to treatment due to the high incidence of malnutrition in this population group. Patients who experience neurotoxicity are also at high risk of malnutrition and are likely to require nasogastric enteral feeding for a period to prevent significant WL. Further research on the impact of neurotoxicity on nutritional status, and longer term follow up on the nutritional impact of CAR T-cell therapy is required to influence future dietetic practice in this field.
Udo Holtick, Anja Jühling, Philipp Gödel, et al.
Conclusions: Our data demonstrates that a standard leukapheresis is effective to collect sufficient CD3 T-cells for CAR T-cell production. Patients can be safely and successfully collected with CD3 counts down to 50-100 CD3 T-cells/ µl peripheral blood. Follow-up of completed infusion rates and reasons for infusion failure are currently under investigation and will be presented.
R. Ram R. Gold O. Amit, et al.
Conclusions: This pivotal clinical and quality management system is an ongoing process and is obliged to maximize patients and products´ safety and performance.
Georg-Nikolaus Franke, Eberhard Schleyer, Konstantin Weibl, et al.
Conclusions: Bridging eligible patients from LA to CD19 CAR T-cell infusion remains a challenge. Patients with a CAR T score >4 should be considered to be at higher risk for complications. The proposed score has to be evaluated in a larger cohort.
Flore Durieux, Nicolas Simon, Héloïse Henry, et al.
Conclusions: During the study period, some patients were not reconciled due to a lack of staff in the department, particularly at the beginning of the year. Usually, the studied population takes few drugs. Therefore, some patients took more than 10 drugs. In this study, drug adherence was often minimal as shown in a literature review that evaluates drug adherence in patients receiving hematopoietic stem cell transplantation1 . This shows that reconciliation activity for these patients appears essential in order to review treatments, insist on medication adherence and to prevent the risks of drug-drug interaction, especially with the conditioning regimen. The data from this preliminary study need to be confirmed on a larger population.