Jeremy S. Abramson, MD, MMSc
Liso-cel (lisocabtagene maraleucel), formally known as JCAR017, induced an objective response rate (ORR) of 81% with a complete remission (CR) rate of 63% in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), according to updated findings from the TRANSCEND trial presented at the 2017 ASH Annual Meeting.
At the 3-month assessment for the dose being used in an ongoing pivotal trial for liso-cel, the ORR was 74% with a CR rate of 68% (95% CI, 43%-87%). By month 6, the ORR and CR rates were both 50% in this group (95% CI, 23%-77%). There were comparatively low rates of severe cytokine release syndrome (CRS) and neurotoxicity in the trial, suggesting the potential for outpatient administration, according to lead investigator Jeremy S. Abramson, MD, MMSc.
"Lisocabtagene maraleucel, a CD19-directed CAR T cell product with a fixed defined composition, shows potent and durable remissions in high-risk diffuse large B-cell lymphoma," said Abramson, from the Massachusetts General Hospital Cancer Center. "The toxicity with liso-cell is overall manageable and low."
Liso-cel consists of a defined CD4 and CD8 composition and 4-1BB costimulatory domain. The defined composition allows administration of a precise dose, Abramson noted. At study entry, patients underwent leukapheresis followed by manufacturing of JCAR017. The expected time from apheresis to infusion was less than 3 weeks, he added, and the treatment was successfully manufactured for 98% of patients.
Prior to CAR T cell infusion, patients received lymphodepleting fludarabine (30 mg/m2
) and cyclophosphamide (300 mg/m2
) daily for 3 days. In a dose findings portion of the study, 2 dose levels (DL) were utilized: 5 x 107
cells (DL1) as a single- or double-dose and liso-cel at 1 x 108
cells (DL2) as a single-dose. After the dose finding portion of the study, DL1 and DL2 as single infusions were further studied in a core assessment, with DL2 moving into the pivotal cohort focused on DLBCL.
Overall, 91 patients were enrolled in the full study, with 67 treated specifically in the core assessment. There were 40 patients treated with the dose selected for the pivotal cohort. Five patients were successfully treated in the outpatient setting.
In the core assessment, the median age of patients was 60 years (range, 20-82), with 36% ≥65 years of age. Two-thirds of patients (66%) were chemorefractory, and patients had received a median of 3 prior therapies (range, 1-8) with 51% having never achieved a CR to prior therapy. Forty-two percent of patients had received prior stem cell transplant. "Patients with prior allotransplant are not being included in the pivotal cohort," Abramson noted.
The most common B-cell subtype was DLBCL, NOS de novo (76%). The remainder of patients had DLBCL that was transformed from follicular lymphoma (tFL). Twenty-four percent of patients had double- or triple-hit lymphoma. The full study also included patients with marginal zone lymphoma (MZL), transformed chronic lymphocytic leukemia (tCLL), primary mediastinal B-cell lymphoma (PMBCL), and grade 3b follicular lymphoma (FL3B).
Efficacy data were available for 88 patients in the full trial. Across the full cohort, the ORR was 74% and the CR rate was 52%. At the 6-month analysis, the ORR was 35% and the CR rate was 31%. For those with DLBCL, NOS (n = 57), the ORR at 6 months was 35% and the CR rate was 32%. In the tFL group (n = 19), the 6-month ORR was 50% and the CR rate was 40%. In the non-core subgroup, those with tCLL and MZL (n = 10) did not respond to liso-cel.
In those with relapsed/refractory DLBCL regardless of B-cell subtype (n = 65), the best ORR was 80% and the CR rate was 55% across all doses. At 6 months, the ORR was 47% and the CR rate was 42%. In the DL1 group, the 6-month ORR and CR were 40% and 30%, respectively.
Responses to liso-cel were seen across all subgroups of DLBCL, particularly in those at high risk. Liso-cel elicited an ORR of 84.6% in those with double/triple hit lymphoma and an ORR of 84.6% in those who relapsed on stem cell transplant after <12 months. The ORR was 73.1% in patients who had never achieved a CR to prior therapy. Responses were similar between those who were chemosensitive and chemorefractory.
In the full cohort, the median duration of CR was 9.2 months and the median duration of ORR was 5.0 months. In the core study population, the median duration of CR was not yet reached. The median duration of ORR was 9.2 months. The duration of partial response was 2.1 months in each group.
"In those patients who were evaluable at 3 months in remission and then evaluable at 6 months we saw 80% of patients with a CR at 3 months continue to have a CR at 6 months," Abramson said. "In patients evaluable beyond 6 months, we see 92% of those patients in ongoing remission at the time of their last assessment."