CAR T-Cell Therapies: New Research and Updates from Pivotal Trials

More Info in the ASH Press release

Webcasts at the bottom

299 Comparison of Efficacy and Toxicity of CD19-Specific Chimeric Antigen Receptor T-Cells Alone or in Combination with Ibrutinib for Relapsed and/or Refractory CLL


Jordan Gauthier, et al

Conclusion Administration of ibrutinib from 2 weeks before leukapheresis until 3 months after JCAR014 was well tolerated in most pts. This approach might decrease the incidence of severe CRS and improve responses in pts with R/R CLL.

https://ash.confex.com/ash/2018/webprogram/Paper111061.html

 

556 Checkpoint Inhibitors Augment CD19-Directed Chimeric Antigen Receptor (CAR) T Cell Therapy in Relapsed B-Cell Acute Lymphoblastic Leukemia

Shannon Maude, et al.

Discussion: T cell exhaustion or activation induced CAR T death (AICD) has been suspected to contribute to poor persistence of CAR T cells. We hypothesized that the PD-1 checkpoint pathway may be involved in CAR T cell exhaustion in some cases, which may be overcome by checkpoint inhibition. Here, promising responses were specifically seen in those with early B-cell recovery and bulky extramedullary disease. In contrast, PD-1 inhibition had partial, but no durable, effect in the four B-ALL patients with poor initial marrow response to CAR T cell therapy alone, suggesting a different mechanism such as AICD may be responsible for poor initial responses. No unexpected or fatal toxicities were seen. This cohort shows initial evidence that checkpoint inhibitors can be used effectively and safely with CAR T cell therapy in children with relapsed B-ALL, and that this strategy may augment CAR T cell effect and persistence.

https://ash.confex.com/ash/2018/webprogram/Paper112572.html

 

895 Updated Analysis of the Efficacy and Safety of Tisagenlecleucel in Pediatric and Young Adult Patients with Relapsed/Refractory (r/r) Acute Lymphoblastic Leukemia

Stephan A. Grupp, et al.

CONCLUSIONS

With longer follow-up, the ELIANA study continues to confirm the efficacy of a single infusion of tisagenlecleucel in pediatric and young adults with ALL without additional therapy. AEs were effectively and reproducibly managed globally by appropriately trained personnel at study sites. The achievement of high overall response rates and deep remissions, in combination with the median duration of response and overall survival not being reached, further corroborate previously reported results.

https://ash.confex.com/ash/2018/webprogram/Paper112599.html

 

1684 Sustained Disease Control for Adult Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma: An Updated Analysis of Juliet, a Global Pivotal Phase 2 Trial of Tisagenlecleucel

Richard Thomas T. Maziarz, et al.

CONCLUSION

Results from this longer-term follow-up show that tisagenlecleucel produced high response rates and durable responses in a cohort of heavily pretreated adult patients with r/r DLBCL. Efficacy was consistent in all predefined subgroups, including elderly patients, patients with r/r disease, and other clinical or biological subgroups expected to have a worse prognosis with available treatments, as demonstrated by similar and sustained DOR and OS following tisagenlecleucel treatment.


https://ash.confex.com/ash/2018/webprogram/Paper115252.html

NEJM: ORIGINAL ARTICLE

Tisagenlecleucel in Adult Relapsed or Refractory Diffuse Large B-Cell Lymphoma

S.J. Schuster and Others

967 Long-Term Follow-up after SCRI-CAR19v1 Reveals Late Recurrences As Well As a Survival Advantage to Consolidation with HCT after CAR T Cell Induced Remission

Corinne Summers, et al.

Conclusions: We demonstrate a trend towards improved LFS for subjects without a history of HCT who undergo a consolidative HCT following CD19 CAR T cell therapy on PLAT-02. In addition, HCT appears to benefit subjects who attain a CR but are at increased risk of relapse with short-term BCA. Currently, the benefit of second HCT following CD19 CAR T cell therapy is unclear and may be restricted to those that have short functional persistence of SCRI-CAR19v1. Late relapses after SCRI-CAR19v1 have only occurred in those without consolidative HCT, but longer follow up is needed to confirm these findings.


https://ash.confex.com/ash/2018/webprogram/Paper115599.html