LARGE & DIFUSE LARGE B-CELL & OTHER B-CELL LYMPHOMAS
Michael Wang, Javier Munoz, Andre Goy, et al.
Conclusions: With ≥ 1 year of follow-up, KTE-X19 demonstrated significant and durable clinical benefit and a manageable safety profile in patients with R/R MCL for whom there are no curative treatment options.
Jeremy Abramson, M. Lia Palomba, Leo Gordon, et al.
Conclusions: Liso-cel showed durable clinical activity with a favorable safety profile across relapsed/refractory LBCL histologic subgroups and in patients with poor prognosis, including chemotherapy refractory, older age, comorbidities, and high tumor burden. Incidence of severe CRS and NEs was low, with late onset, allowing for outpatient administration.
Jason Westin, Constantine Tam, Peter Borchmann, et al.
Conclusions: Multivariate analyses identified that high levels of pre-infusion LDH (a known marker of tumor burden, metabolic activity, and disease aggressiveness) were associated with NRs at month 3 and worse PFS/OS. Pre-infusion grade 3/4 thrombocytopenia and grade 3/4 NE were also associated with poor efficacy outcomes. The highest serum biomarker profiles post-infusion appeared to associate with patients with severe CRS who were also NRs. These analyses suggest that a subset of patients with aggressive disease at infusion and/or patients with severe CRS/NE had poorer outcomes in the JULIET trial, and may reinforce the rationale for current and future directions of using CAR-T cell therapy in an earlier line of therapy (during less aggressive/less advanced disease), optimizing patient care, and developing interventions to prevent severe CRS and/or NE.
Sattva Neelapu, Frederick Locke, Nancy Bartlett, et al.
Conclusions: This standardized analysis of ZUMA-1 and SCHOLAR-1 indicates that treatment with axi-cel in this selected population increased odds of CR and reduced the risk of death versus standard salvage regimens in an unselected population. Although limited by retrospective evaluation and cross-study comparisons, these results support those of the published literature indicating that axi-cel is a highly effective treatment option for patients with refractory LBCL.
R. Alonso-Trillo S. Roni J. Flynn, et al.
Conclusions: In this cohort of 52 evaluable patients with R/R DLBCL treated with commercial CAR T cells, we showed that the international prognostic indexes (IPI and a-IPI) can predict survival outcomes. In addition, the IPI determined pre-leukapheresis can also predict neurotoxicity in this patient population. These results may help with patient selection as well toxicity mitigation in high risk patients with R/R DLBCL. Results for HCT-CI need further validation due to the small sample of evaluable patients.
Ulrich Jäeger, Nina Worel, Joseph McGuirk, et al.
Conclusions: PD-1 blockade with pembrolizumab was feasible and showed a manageable safety profile in the first 4 patients. No DLTs and no clinically significant exacerbation of AEs were observed.
G. Iacoboni E. Catala J. Sanchez Pina, et al.
Conclusions: Tisagenlecleucel can achieve disease response with a good safety profile in patients with R/R DLBCL treated in the real-world setting in a European country.
Rawan Faramand, Michael Jain, Verena Staedtke, et al.
Conclusions: We have confirmed that patients' cytokine profile at baseline as related to the tumor microenvironment plays a key role in toxicity and provided insight into a novel mechanism of toxicity involving myeloid cells and catecholamines. Emerging biologic data is vital for designing clinical trials aimed at further reducing the rates of severe toxicities.
Max Topp, Tom van Meerten, Roch Houot, et al.
Conclusions: Earlier steroid use may reduce the rates of CAR T cell treatment-related CRS and NEs without affecting efficacy. Conclusions are limited by the nonrandomized study design and differences in population sizes and baseline characteristics between cohorts. Optimizing AE management is important to improve the benefit-risk profile of CAR T cell therapy.
N. Gazeau D. Beauvais S. Manier, et al.
Conclusions: Nivo seemed to be effective and safe in a small number of patients who did not achieve CR after CAR T-cell therapy.
Houli Zhao, Yongxian Hu, Wei Ding, et al.
Conclusions: CtDNA profiling is a promising new technique for surveillance of MRD in DLBCL after CAR-T therapy. In some cases, ctDNA can predict the disease progression earlier than PET-CT scan. A much number of abnormal genes in baseline particularly XPO1 E571K mutation may be a poor prognostic factor after CAR-T therapy in DLBCL.
Robin Sanderson, Reuben Benjamin, Piers Patten, et al.
Conclusions: CD19 CAR T cells have been safely delivered in the NHS and our large single centre cohort demonstrates lower toxicity with axi-cel, particularly of ICANS then described in a recent large CIBMTR cohort (Pasquini et al. ASH 2019). Initial response rates are high although PFS is lower than expected. Interestingly, 3+ prior therapies were associated with inferior PFS, implying patients may benefit from earlier referral for consideration of CAR T cells. By EBMT further follow-up will allow 6-month outcomes and predictors of response to be presented.
Nela Klein-González, E. Azucena González-Navarro, Ariadna Bartoló-Ibars, et al.
Conclusions: These data suggest the importance of the immunogenicity induced by CART-cell therapies. Immune monitoring should include the assessment of humoral response, especially before considering a second dose after relapse.
Katia Beider, Michal J. Besser, Jacob Schachter, et al.
Conclusions: Overall, these results elucidate in part the mechanisms of CAR T traffic, immunosuppressive responses as well as induction of T cell senescence/exhaustion that most probably downregulate CAR T effectiveness as observed in non-responding pts.
Catherine Hockings, Andrea Kuhnl, Shu Wong, et al.
Conclusions: Many patients experience late cytopenias following CAR-T, therefore close monitoring of blood counts is required following discharge. Persistent cytopenias on discharge appear to correlate with prior bridging chemotherapy and are not associated with responses at 3 month follow up. Further work, including correlation with cytokine levels, is needed to determine the cause of late cytopenias. With maturation and expansion of the patient cohort we hope to determine whether cytopenias may be related to expansion and persistence of CAR-T and correlate with positive outcomes.
Ahmed Abdelhady, Hidefumi Hiramatsu, Takanori Teshima, et al.
Conclusions: Asian and non-Asian patient populations in both indications were comparable with respect to safety, efficacy, dose-response, product attributes, and cellular kinetics of tisagenlecleucel.
R. Ram D. Hagin T. Freund, et al.
Conclusions: While there remains insufficient data to solidly confirm our hypothesis, it is reasonable to assume that pre-lymphopheresis disease duration and treatment history may affect pheresis product, which in-turn, determines the final CAR T-cell product and response to treatment. Preliminary data from our small cohort suggests that pre-pheresis bendamustine treatment is associated with more mature, activated and exhausted CD4 T-cell phenotype. Improved phenotyping to include additional exhaustion markers, as well as follow-up post CAR T-cell infusion (by evaluating peripheral blood CD19-Ig binding T cells) is ongoing.
Maria-Luisa Schubert, Sascha Dietrich, Anita Schmitt, et al.
Conclusions: Therapy with CARTs manufactured from recipient-derived leukapheresis products after prior alloHCT was feasible, safe and efficient. Therefore, CARTs as salvage treatment for patients with B-cell lymphoma relapsing after alloHCT constitute a justifiable treatment option. Cytopenia as a result of multiple myelotoxic treatments needs to be carefully monitored.
M. Melody S. Gandhi Z. Abdel Rahman, et al.
Conclusions: Hypoalbuminemia does not have a significant impact on the outcomes of axi-cel therapy, including OS or the incidence of CRS or neurotoxicity. Large multicenter clinical trials are needed to validate these findings.