Real-world characteristics of T-cell apheresis and clinical response to tisagenlecleucel in B-cell lymphoma.
Ontology highlight
ABSTRACT:
SUBMITTER: Cuffel A
PROVIDER: S-EPMC9636323 | biostudies-literature | 2022 Aug
REPOSITORIES: biostudies-literature
Publications
Real-world characteristics of T-cell apheresis and clinical response to tisagenlecleucel in B-cell lymphoma.
Cuffel Alexis A Allain Vincent V Faivre Lionel L Di Blasi Roberta R Morin Florence F Vercellino Laetitia L Chevalier Mathieu F MF Desnoyer Aude A de Jorna Romain R Madelaine Isabelle I Parquet Nathalie N Brignier Anne C AC Thieblemont Catherine C Larghero Jerome J Caillat-Zucman Sophie S Mebarki Miryam M
Blood advances 20220801 15
Similar Datasets
Project description:Tisagenlecleucel (tisa-cel) is a second-generation autologous CD19-targeted chimeric antigen receptor (CAR) T-cell therapy approved for relapsed/refractory (R/R) large B-cell lymphoma (LBCL). The approval was based on the results of phase II JULIET trial, with a best overall response rate (ORR) and complete response (CR) rate in infused patients of 52% and 40%, respectively. We report outcomes with tisa-cel in the standard-of-care (SOC) setting for R/R LBCL. Data from all patients with R/R LBCL who underwent leukapheresis from December 2018 until June 2020 with the intent to receive SOC tisa-cel were retrospectively collected at 10 Spanish institutions. Toxicities were graded according to ASTCT criteria and responses were assessed as per Lugano 2014 classification. Of 91 patients who underwent leukapheresis, 75 (82%) received tisa-cel therapy. Grade 3 or higher cytokine release syndrome and neurotoxicity occurred in 5% and 1%, respectively; non-relapse mortality was 4%. Among the infused patients, best ORR and CR were 60% and 32%, respectively, with a median duration of response of 8.9 months. With a median follow-up of 14.1 months from CAR T-cell infusion, median progression-free survival and overall survival were 3 months and 10.7 months, respectively. At 12 months, patients in CR at first disease evaluation had a PFS of 87% and OS of 93%. Patients with an elevated lactate dehydrogenase showed a shorter PFS and OS on multivariate analysis. Treatment with tisa-cel for patients with relapsed/refractory LBCL in a European SOC setting showed a manageable safety profile and durable complete responses.
| S-EPMC8124109 | biostudies-literature
Project description: Not available
| S-EPMC11808862 | biostudies-literature
Project description:Aim: To contextualize the effectiveness of tisagenlecleucel versus real-world standard of care (SoC) in relapsed/refractory follicular lymphoma. Materials & methods: A retrospective indirect matched comparison study using data from the phase II ELARA trial and the US Flatiron Health Research Database. Results: Complete response rate was 69.1 versus 17.7% and the overall response rate was 85.6 versus 58.1% in tisagenlecleucel versus SoC, post weighting by odds. For overall survival, an estimated reduction in the risk of death was observed in favor of tisagenlecleucel over SoC. The hazard ratio for progression-free survival was 0.45 (95% CI: 0.26, 0.88), and for time-to-next treatment was 0.34 (95% CI: 0.15, 0.78) with tisagenlecleucel versus SoC. Conclusion: A consistent trend toward improved efficacy end points was observed in favor of tisagenlecleucel versus SoC.
| S-EPMC10508300 | biostudies-literature
Project description:Tisagenlecleucel is a CD19 chimeric antigen receptor (CAR) T-cell therapy approved for treatment of pediatric and young adult patients with relapsed/refractory acute lymphoblastic leukemia (ALL) and adults with non-Hodgkin lymphoma (NHL). The initial experience with tisagenlecleucel in a real-world setting from a cellular therapy registry is presented here. As of January 2020, 511 patients were enrolled from 73 centers, and 410 patients had follow-up data reported (ALL, n = 255; NHL, n = 155), with a median follow-up of 13.4 and 11.9 months for ALL and NHL, respectively. Among patients with ALL, the initial complete remission (CR) rate was 85.5%. Twelve-month duration of response (DOR), event-free survival, and overall survival (OS) rates were 60.9%, 52.4%, and 77.2%, respectively. Among adults with NHL, the best overall response rate was 61.8%, including an initial CR rate of 39.5%. Six-month DOR, progression-free survival, and OS rates were 55.3%, 38.7%, and 70.7%, respectively. Grade ≥3 cytokine release syndrome and neurotoxicity were reported in 11.6% and 7.5% of all patients, respectively. Similar outcomes were observed in patients with in-specification and out-of-specification products as a result of viability <80% (range, 61% to 79%). This first report of tisagenlecleucel in the real-world setting demonstrates outcomes with similar efficacy and improved safety compared with those seen in the pivotal trials.
| S-EPMC7656920 | biostudies-literature
Project description:Axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) have both demonstrated impressive clinical activity in relapsed/refractory (R/R) diffuse large B cell lymphoma (DLBCL). In this study, we analyzed the outcome of 809 patients with R/R DLBCL after two or more previous lines of treatment who had a commercial chimeric antigen receptor (CAR) T cells order for axi-cel or tisa-cel and were registered in the retrospective French DESCAR-T registry study ( NCT04328298 ). After 1:1 propensity score matching (n = 418), the best overall response rate/complete response rate (ORR/CRR) was 80%/60% versus 66%/42% for patients treated with axi-cel compared to tisa-cel, respectively (P < 0.001 for both ORR and CRR comparisons). After a median follow-up of 11.7 months, the 1-year progression-free survival was 46.6% for axi-cel and 33.2% for tisa-cel (hazard ratio (HR) = 0.61; 95% confidence interval (CI), 0.46-0.79; P = 0.0003). Overall survival (OS) was also significantly improved after axi-cel infusion compared to after tisa-cel infusion (1-year OS 63.5% versus 48.8%; HR = 0.63; 95% CI, 0.45-0.88; P = 0.0072). Similar findings were observed using the inverse probability of treatment weighting statistical approach. Grade 1-2 cytokine release syndrome was significantly more frequent with axi-cel than with tisa-cel, but no significant difference was observed for grade ≥3. Regarding immune effector cell-associated neurotoxicity syndrome (ICANS), both grade 1-2 and grade ≥3 ICANS were significantly more frequent with axi-cel than with tisa-cel. In conclusion, our matched comparison study supports a higher efficacy and also a higher toxicity of axi-cel compared to tisa-cel in the third or more treatment line for R/R DLBCL.
| S-EPMC9556323 | biostudies-literature
Project description: Not available
| S-EPMC11334869 | biostudies-literature
Project description:Ibrutinib is highly effective in patients with relapsed or refractory mantle cell lymphoma (MCL) in major clinical trials. Although there has been a dramatic improvement in survival outcomes in the salvage setting, nonresponders to ibrutinib have a bleak prognosis. Therefore, this retrospective study was conducted to identify the most appropriate therapeutic strategy and prognosis-related factors to predict the response of patients with relapsed or refractory MCL to ibrutinib monotherapy. Thirty-three consecutive refractory or relapsed MCL patients treated with ibrutinib were analyzed in this study. The median overall survival (OS) and progression-free survival (PFS) after initiation of ibrutinib were 35.1 months and 27.4 months, respectively. Risk factor analysis showed that high risk according to the Mantle Cell Lymphoma International Prognostic Index (MIPI) and nonresponse to ibrutinib at the first three cycles were significantly associated with inferior OS. Poor PFS was associated with high-risk biologic MIPI, prior bendamustine exposure, and nonresponse to ibrutinib during the first three cycles. After ibrutinib failure, primary nonresponders had poorer OS and PFS than inconsistent responders. The overall response rate for the first salvage therapy was only 33%, with a median TTP of 3.2 months. There was no effective therapeutic strategy except for allogeneic hematopoietic stem cell transplantation (allo-HSCT). Although ibrutinib responders exhibited favorable survival outcomes, nonresponders had a dismal prognosis. To overcome these limitations, it may be necessary to modify therapeutic strategies, such as selecting inconsistent responders for earlier allo-HSCT.
| S-EPMC6853811 | biostudies-literature
Project description:Chimeric antigen receptor (CAR) T cells targeting CD19 have emerged as a leading engineered T-cell therapy for relapsed/refractory B-cell non-Hodgkin lymphoma. The phase 1/2 clinical trials that led to US Food and Drug Administration approval excluded patients with central nervous system (CNS) involvement, due to strict eligibility criteria. Here, we report on our institutional experience with 8 secondary CNS lymphoma patients treated with commercial tisagenlecleucel. No patient experienced greater than grade 1 neurotoxicity, and no patient required tocilizumab or steroids for CAR T-cell-mediated toxicities. Biomarker analysis suggested CAR T-cell expansion, despite the absence of systemic disease, and early response assessments demonstrated activity of IV infused CAR T cells within the CNS space.
| S-EPMC7022436 | biostudies-literature
Project description:Mantle cell lymphoma (MCL) is considered incurable with the available chemoimmunotherapy approaches, and therefore, newer effective targeted therapies such as Bruton tyrosine kinase (BTK) inhibitors are increasingly used in MCL as chronic suppressive therapy, especially in the elderly. We aimed to describe the treatment patterns in MCL at different lines of therapy with a focus on BTK inhibitor use and compare outcomes with known prognostic factors using a nationwide Flatiron Health electronic health record-derived de-identified database. We analyzed patient-level data from the period of 2011 to 2021. In this study of 4336 patients with MCL, we found that bendamustine plus rituximab chemotherapy was the most commonly used frontline regimen (42%). Maintenance rituximab or consolidative autologous stem cell transplant (ASCT) was administered to 31% of all patients. Also, for patients who received ASCT as consolidation therapy, only 34% subsequently received rituximab maintenance. BTK inhibitors were the most preferred agents in second or later lines of therapy (n = 933, 57%), followed by bortezomib, lenalidomide, and venetoclax, respectively. Among patients treated with BTK inhibitors, the median real-world overall survival (rwOS) was 35 months (95% confidence interval [CI], 27-50), 24 months (95% CI, 22-30), and 18 months (95% CI, 14-21) for first line, second line, and third or later line of therapy, respectively. Patients with a deletion 17p/TP53 mutation and blastoid variant MCL had poor outcomes; however, BTK inhibitors appeared to mitigate the negative influence of del17p/TP53-mutated MCL with a hazard ratio of 1.17 (95% CI, 0.88-1.55) on multivariable analysis.
| S-EPMC9327535 | biostudies-literature
Project description:Tisagenlecleucel has revolutionized the pharmacological approach of relapsed or refractory B-cell acute lymphoblastic leukaemialeukaemia in paediatrics. The safety profile of tisagenlecleucel still needs to be better defined. The aim of this study was a post-marketing evaluation of the safety of tisagenlecleucel through the analysis of the Eudravigilance database with focus on the paediatric population. From 2017 to 2020, one third of Individual Case Safety Reports referring to tisagenlecleucel (117/364) have been collected in paediatrics, on average nine year-old boys. Overall, 92% of the638 adverse events were serious and caused or prolonged hospitalisation. A total of 55 adverse events presented a fatal outcome, mainly due to progression of malignant neoplasm (N = 10; 18.2%), recurrence of acute lymphocytic leukaemia (N = 6; 10.9%) or occurrence of acute lymphocytic leukaemia (N = 5; 9.1%). Cytokine release syndrome was commonly reported after tisagenlecleucel infusion (54/638), followed by pyrexia (45/638) and hypotension (27/638). Only 18/638 events referred to neurotoxicity, none of them resulted in death. More than one third of cases (41/117) were suggestive of therapeutic failure. This first post-marketing analysis confirms pre-approval evidence of the safety profile of tisagenlecleucel in paediatrics. Since only a few years of marketing is available, further followed-up studies need to be performed to investigate longer-term safety of tisagenlecleucel.
| S-EPMC7558916 | biostudies-literature