LARGE & DIFUSE LARGE B-CELL & OTHER B-CELL LYMPHOMAS

O036 - KTE-X19, AN ANTI-CD19 CHIMERIC ANTIGEN RECEPTOR (CAR) T CELL THERAPY, IN PATIENTS WITH RELAPSED/REFRACTORY (R/R) MANTLE CELL LYMPHOMA (MCL): RESULTS FROM PHASE 2 OF ZUMA-2

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.

 

O037 - SAFETY AND EFFICACY RESULTS FROM TRANSCEND NHL 001, A MULTICENTER PHASE 1 STUDY OF LISOCABTAGENE MARALEUCEL (LISO-CEL) IN RELAPSED/REFRACTORY LARGE B-CELL LYMPHOMA

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.

 

O042 - CORRELATIVE ANALYSES OF PATIENT AND CLINICAL CHARACTERISTICS ASSOCIATED WITH EFFICACY IN TISAGENLECLEUCEL-TREATED RELAPSED/REFRACTORY DIFFUSE LARGE B-CELL LYMPHOMA PATIENTS IN THE JULIET TRIAL

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.

 

O045 - A COMPARISON OF 2-YEAR OUTCOMES IN ZUMA-1 (AXICABTAGENE CILOLEUCEL; AXI-CEL) AND SCHOLAR-1 IN PATIENTS WITH REFRACTORY LARGE B CELL LYMPHOMA (LBCL)

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.

 

O047 - INTERNATIONAL PROGNOSTIC INDEX PREDICTS OUTCOMES IN PATIENTS WITH RELAPSED AND REFRACTORY LARGE DIFFUSE B CELL LYMPHOMA TREATED WITH COMMERCIAL CAR T CELLS

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.

 

O048 - THE PHASE 1B PORTIA STUDY: SAFETY AND EFFICACY OF TISAGENLECLEUCEL PLUS PEMBROLIZUMAB IN PATIENTS WITH RELAPSED/REFRACTORY DIFFUSE LARGE B-CELL LYMPHOMA

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.

 

O049 - REAL-WORLD EVIDENCE OF THE USE OF TISAGENLECLEUCEL FOR PATIENTS WITH RELAPSED/REFRACTORY AGRESSIVE B-CELL LYMPHOMAS. THE SPANISH EXPERIENCE

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.

 

A080 - CORRELATIVE MARKERS OF TOXICITY IN PATIENTS WITH DLBCL TREATED WITH CD19 CAR T CELL THERAPY

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.

 

A081 - EARLIER STEROID USE WITH AXICABTAGENE CILOLEUCEL (AXI-CEL) IN PATIENTS WITH RELAPSED/REFRACTORY LARGE B CELL LYMPHOMA (R/R LBCL)

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.

 

A084 - NIVOLUMAB AS SALVAGE THERAPY IN PATIENTS WHO FAILED TO ACHIEVE COMPLETE REMISSION AFTER ANTI-CD19 CAR T-CELL THERAPY FOR DLBCL

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.

 

A085 - SURVEILLANCE OF MINIMAL RESIDUAL DISEASE (MRD) IN DIFFUSE LARGE B CELL LYMPHOMA (DLBCL) BY CIRCULATING TUMOR DNA (CTDNA) PROFILING AFTER CHIMERIC ANTIGEN RECEPTOR T (CAR-T)

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.

 

A088 - AXICABTAGENE CILOLEUCEL CD19 CAR T-CELLS FOR RELAPSED/REFRACTORY LARGE B-CELL LYMPHOMA: REAL-WORLD OUTCOMES, TOXICITY AND PREDICTORS OF RESPONSE FROM A PROSPECTIVE UK COHORT

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.

 

A091 - HUMORAL IMMUNE RESPONSE IN PATIENTS WITH CD19-POSITIVE RELAPSED/REFRACTORY B-CELL MALIGNANCIES RECRUITED INTO THE CART19-BE-01 CLINICAL TRIAL, AN ACADEMIC CAR19

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.

 

A093 - SENESCENT/EXHAUSTED PHENOTYPE OF CD19-TARGETED CAR-T CELLS AND IMMUNOREGULATORY ENVIRONMENT CORRELATE WITH REDUCED RESPONSE TO CAR-T CELL THERAPY IN RELAPSED/REFRACTORY B CELL MALIGNANCIES

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.

 

A094 - CHARACTERISATION OF EARLY AND LATE CYTOPENIAS IN LYMPHOMA PATIENTS FOLLOWING TREATMENT WITH ANTI-CD19 CAR-T THERAPY

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.

 

A096 - IMPACT OF ETHNICITY IN R/R DLBCL AND B-CELL ALL PATIENTS TREATED WITH TISAGENLECLEUCEL

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.

 

A097 - IMPACT OF DIFFERENT CHEMOTHERAPY REGIMENS AND DURATION OF DLBCL ON LYMPHOPHERESIS AND CAR-T T-CELL IMMUNOPHENOTYPING

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.

 

A104 - CAR T CELL THERAPY DIRECTED AGAINST CD19 IN PATIENTS WITH B-CELL LYMPHOMA AFTER AN ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION (ALLOHCT) IS FEASIBLE AND SAFE

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.

Disclosure:

 

A106 - BASELINE HYPOALBUMINEMIA DOES NOT APPEAR TO BE AN ADVERSE PROGNOSTIC FACTOR IN PATIENTS WITH RELAPSE/REFRACTORY B-CELL LYMPHOMAS TREATED WITH AXICABTAGENE CILOLEUCEL (AXI-CEL)

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.