In the dose level 2 cohort, the ORR was 70%; the CR rate was 20% (n = 2), the PR rate was 50% (n = 5), the SD rate was 20% (n = 2), and the PD rate was 10% (n = 1).
Response was assessed at 30 days following treatment with liso-cel. Across both cohorts, the ORR was 75% (n = 12) with a 31.3% CR rate (n = 5) and a 43.8% PR rate (n = 7). In the dose level 1 cohort, the ORR was still 100% with a 50% CR and PR rate (n = 3 each). The ORR, CR rate, and PR rate were 60% (n = 6), 20% (n = 2), and 40% (n = 4), respectively, in the dose level 2 cohort.
Efficacy was again evaluated at 3 months posttreatment with liso-cel. Overall, the ORR was 80% (n = 8), the CR rate was 50% (n = 5), and the PR rate was 30% (n = 3). The ORR was 83.3% (n = 5), the CR rate was 50% (n = 3), and 33.3% (n = 2) in the dose level 1 cohort. In the dose level 2 group, the ORR was 75% (n = 3), followed by a 50% CR rate (n = 2) and 25% PR rate (n = 1).
“I think it is a little bit too early and short to say that there is a dose-response correlation at this point; this is certainly something we will be following over time,” said Siddiqi.
Minimal residual disease was evaluated at 10-4 sensitivity via 6-color flow cytometry using peripheral blood and at 10-6 sensitivity by clonoSEQ deep sequencing of bone marrow aspirates. Eleven patients (73.3%) had uMRD sensitivity 10-4 (uMRD4) via flow cytometry at day 30, all of whom continue to remain undetectable at the most recent follow-up, Siddiqi noted. All 5 patients with a post-dose follow-up at 6 months continue to maintain uMRD4 response.
The pharmacokinetic/pharmacodynamic profile showed that the median time to peak expansion for all patients was 16 days (range, 4-30). Results of a correlative biomarker analysis, in which 38 cytokines were analyzed in 13 patients within the first 30 days of treatment, showed that interleukin-16 and tumor necrosis factor were elevated before onset in 3 of 4 patients who experienced grade 2/3 neurologic events.
Siddiqi noted that following an analysis of dose-escalation data and determining the recommended phase II dose, the phase II portion of the trial will likely open for accrual in the first half of 2019.
Siddiqi T, Soumerai JD, Wierda WG, et al. Rapid MRD-negative responses in patients with relapsed/refractory CLL treated with liso-cel, a CD19-directed CAR T-cell product: preliminary results from TRANSCEND CLL 004, a phase 1/2 study including patients with high-risk disease previously treated with ibrutinib. Presented at: 2018 ASH Annual Meeting and Exposition; December 1-4, 2018; San Diego. Abstract 300.
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