626. Aggressive Lymphoma (Diffuse Large B-Cell and Other Aggressive B-Cell Non-Hodgkin Lymphomas)—Results from Prospective Clinical Trials: Immune-Based Therapeutic Approaches


Primary Analysis of Juliet: A Global, Pivotal, Phase 2 Trial of CTL019 in Adult Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma

Stephen J. Schuster, et al.

The authors of the study conclude:

CTL019 produces high response rates with 95% of CRs at 3 months being sustained at 6 months in a cohort of highly pretreated adult patients with r/r DLBCL, results which confirm the findings of our earlier interim analysis. Centralized manufacturing was feasible in the first global study of CAR T cell therapy in DLBCL. CRS and other AEs could be effectively and reproducibly managed by appropriately trained investigators without treatment-related mortality.



Long-Term Follow-up ZUMA-1: A Pivotal Trial of Axicabtagene Ciloleucel (Axi-Cel; KTE-C19) in Patients with Refractory Aggressive Non-Hodgkin Lymphoma (NHL)

Sattva S. Neelapu et al.

The authors of the study conclude:

In the ZUMA-1 study, axi-cel demonstrated significant clinical benefit with manageable AEs in patients with no curative treatment options. Additional long-term efficacy, safety, subgroup, and biomarker associative analyses with a median of 15 months of follow-up will be presented. Loss of CD19 and gain of PD-L1 expression in tumors are identified as possible mechanisms of resistance following axi-cel treatment. These results provide insights into development of novel therapeutic strategies to overcome CD19 CAR T resistance and further improve outcomes in these patients.



A Comparison of One Year Outcomes in ZUMA-1 (axicabtagene ciloleucel) and SCHOLAR-1 in Patients with Refractory, Aggressive Non-Hodgkinlymphoma (NHL)

Sattva S. Neelapu, et al.

The authors of the study conclude:

This standardized comparison between the ZUMA-1 and SCHOLAR-1 studies suggests patients treated with axi-cel experience nearly 10-fold higher odds of CR and a 77% decrease in the risk of death. Despite limitations of this retrospective analysis, these results indicate that axi-cel represents an improved treatment option for patients with refractory, aggressive NHL.



ACTR087, Autologous T Lymphocytes Expressing Antibody Coupled T-Cell Receptors (ACTR), Induces Complete Responses in Patients with Relapsed or Refractory CD20-Positive B-Cell Lymphoma, in Combination with Rituximab

Luke Paul Akard, et al.

The authors of the study conclude:

In the first dose level studied in patients with relapsed/refractory aggressive CD20+ B cell lymphoma, ACTR087 in combination with rituximab induced complete responses with no serious AEs, AEs leading to treatment discontinuation, cytokine-release syndrome, or neurotoxicity. ACTR+ T cells were detectable in all patients and ACTR+ T cells persisted in the presence of continued rituximab administration. These results support the continued dose escalation of ACTR087 in combination with rituximab; dose level 2 enrollment is ongoing and updated data, including correlative biomarkers, will be presented.



High Durable CR Rates in Relapsed/Refractory (R/R) Aggressive B-NHL Treated with the CD19-Directed CAR T Cell Product JCAR017 (TRANSCEND NHL 001): Defined Composition Allows for Dose-Finding and Definition of Pivotal Cohort

Jeremy S. Abramson et al.

The authors of the study conclude:

JCAR017, a defined composition CAR T cell product with precise clinical dosing, resulted in high durable CR rates and an emerging dose:response relationship in heavily pretreated R/R DLBCL. Toxicity was manageable and occurred at a lower rate and later than previously reported for other CAR T cell products. The trial is ongoing; updated enrollment, safety, 3 and 6 month response rates, and OS will be presented.



Effect of Rituximab in Primary Central Nervous System Lymphoma –  results of the Randomized Phase III HOVON 105/ALLG NHL 24 Study

Jacoline Bromberg, et al.

The authors of the study conclude:

in this randomized phase III trial in newly diagnosed PCNSL, the addition of rituximab to HD-MTX-based chemotherapy did not improve response rates, EFS or PFS. Longer follow up is needed to evaluate the effect on overall survival.