On Sunday 3rd June an oral abstract session took place at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting. Abstract 7505 was presented by Jeremy Abramson, Massachusetts General Hospital Cancer Center, Boston, on the updated safety and long term results of the TRANSCEND NHL 001 trial. This was a pivotal trial of the CAR-T therapy (NCT02631044), lisocabtagene maraleucel (JCAR017), in patients with relapsed/refractory (R/R) aggressive non-Hodgkin lymphoma (NHL).
The multicenter trial included three dose-finding cohorts that was expanded into two dose-expansion cohorts and then a pivotal diffuse large B-cell lymphoma (DLBCL) cohort. In total, 102 patients met the full specifications and were included in the study. Additional patients were included in the dose-finding and dose-escalation cohorts including patients with DLBCL that was transformed from chronic lymphocytic leukemia (CLL), marginal zone lymphoma (MZL), or primary mediastinal large cell lymphoma (PMBCL).
Patients and methods:
- Median age = 61 years (range 20–82)
- Dose level 1:
- N = 45 patients received 50 million cells
- N = 6 patients received 50 million cells at a doubled administration 14 days apart
- Dose level 2:
- N = 51 patients were treated with 100 million cells
- Dose level 1:
- Most common grade 3-4 adverse events: cytopenias and fatigue
- Incidence of cytokine release syndrome: 37%
- Incidence of neurologic toxicity: 23%
- Overall response rate: 75%
- Complete remission rate: 55%
- Median duration of response: NR
- 1-year overall survival: NR, although ̴90% of patients who achieved CR remain alive at 12 months
- Subset analysis of patients with DLBCL
- There was no increase in neurotoxicity between dose level 1 and dose level 2 cohorts
- Overall remission rate: 80%
- Complete remission rate: 59%
- Patients treated at dose level 2: 49% are in ongoing remission, 46% are in ongoing CR after six-months
Professor Abramson concluded by saying that “lisocabtagene maraleucel is a CD19-directed CAR T-cell product administered with a defined composition and induced durable responses in high-risk patients with relapsed, refractory aggressive NHL. We see encouraging durable response rates six months and beyond in our core DLBCL dataset population. That includes 49% of patients in ongoing response at six months, and most of those in ongoing complete remission.”
He further added that 93% of patients who achieved the six-month time point, across all dose levels, remained in remission at the last follow up. Based on these findings, lisocabtagene maraleucel is safe with low toxicity.
The study is ongoing to evaluate lisocabtagene maraleucel for outpatient administration, including the pivotal cohort.
Abramson J. et al. Updated safety and long term clinical outcomes in TRANSCEND NHL 001, pivotal trial of lisocabtagene maraleucel (JCAR017) in R/R aggressive NHL. Abstract 7505. 2018 ASCO Annual Meeting, Chicago, Illinois.