626. Aggressive Lymphoma (Diffuse Large B-Cell and Other Aggressive B-Cell Non-Hodgkin Lymphomas)—Results from Prospective Clinical Trials: Results from CAR T-Cell Trials
Conclusion cited from the abstract: Liso-cel demonstrated durable clinical activity with a favorable safety profile in this large study of CAR T cell therapy in R/R large B cell NHL. Low incidence and late onset of CRS and NE allowed for outpatient administration. Clinically meaningful efficacy was observed across histologic subgroups and those with poor prognosis, including pts who were refractory, elderly, comorbid, and/or had high tumor burden.
Conclusion cited from the abstract: In JULIET, tisagenlecleucel CAR-T cell product attributes had no significant impact on efficacy or NE; the total number of activated CD4+ cells infused positively correlated with higher-grade CRS. There is great variability in the product attributes, especially with respect to T-cell phenotypes, though this variability appears to play a minor role on efficacy. Additional analyses with larger data sets are required to confirm these findings. ClinicalTrials.gov Identifier: NCT02445248.
Max Topp, et al.
Conclusion cited from the abstract: Earlier steroid use appears to reduce the rate of CAR T cell Tx-related CRS and NEs in C4 compared with C1+2, without a clinically meaningful impact on efficacy, at a median F/U of 8.7 mo. Conclusions are limited by the non-randomized study design, differences in population sizes and in baseline characteristics between cohorts. Further exploratory analysis will also address the potential confounding effect of bridging therapy. Optimizing AE management is important to improve the benefit-risk profile of CAR T cell therapy.
Conclusion cited from the abstract:
ACTR087+rituximab demonstrated antitumor activity, with observed safety events that are expected with other autologous T-cell products. The time to onset and clinical presentation of severe CRS and neurotoxicity events in this study informed the safety monitoring and adverse reaction management guidance across clinical studies of ACTR T-cell products. Data from this first-in-human study of ACTR087+rituximab confirm the proof of concept and will be used to guide further development for the ACTR platform. Updated clinical data, as well as expanded biomarker correlations to efficacy and safety, will be presented.
Michael D. Jain, et al.
Conclusion cited from the abstract: Lymphoma patients receiving bridging therapy had poorer prognostic factors at baseline and after axi-cel infusion experienced decreased lymphoma-specific and overall survival compared with patients with no bridging. This inferior outcome raises the possibility that bridging therapy may identify a sub-group of lymphoma patients with a different biology, or alternatively, bridging therapy may have an effect on the host or the tumor microenvironment that may impact CAR-T efficacy. With or without bridging, 7% of patients in our series did not receive axi-cel due to lymphoma progression and/or death. In addition, there may have been patients where bridging prevented progression or death prior to axi-cel infusion. Prospective evaluation of different bridging strategies is warranted to determine if any can improve outcomes after axi-cel, and/or if they should be utilized only for patients requiring emergent disease control during the manufacture period.
Kirit M. Ardeshna, et al.
Conclusion cited from the abstract:
AUTO3, a novel bicistronic anti CD19/CD22 CAR T therapy, has a manageable safety profile in combination with Pem. Notable is the lack of severe CRS (0%). The efficacy data with 2/4 patients achieving CR at dose 150 x 10e6 cells is promising. The study continues to enroll patients at higher dose levels of AUTO3 followed by Pem.