On 14 June 2019, at the 24 thEuropean Hematology Association Congress, Tanya Siddiqi presented results of the ongoing phase I/II TRANSCEND CLL 004 study. The study assessed the safety, pharmacokinetics and efficacy of lisocabtagene maraleucel (liso-cel, JCAR017). Liso-cel is an anti-CD19 chimeric antigen receptor (CAR) T-cell product administered as a defined composition of CD4+/CD8+ CAR T-cells.
The primary objectives of the study were safety and determination of the recommended phase II dose.
Patient Characteristics
- Predominantly female patients (52.2%), median age 66
- Patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL)
- Previously received >2 lines of therapy
- ECOG score of <1
Baseline characteristics |
All patients (n = 23) |
DL1 (n = 9) |
DL2 (n = 14) |
|---|---|---|---|
|
Received bridging therapy |
17 (73.9%) |
5 (55.6%) |
12 (85.7%) |
|
High-risk features |
19 (82.6%) |
6 (66.7%) |
13 (92.9%) |
|
Del (17p) |
8 (34.8%) |
3 (33.3%) |
5 (35.7%) |
|
Tp53 mutation |
14 (60.9%) |
4 (44.4%) |
10 (71.4%) |
|
Complex karyotype b |
11 (47.8%) |
5 (55.6%) |
6 (42.9%) |
|
Previous therapy |
5 (2 – 11) |
5 (3 – 8) |
5 (2 – 11) |
|
Prior ibrutinib |
23 (100%) |
9 (100%) |
14 (100%) |
|
Ibrutinib relapsed/refractory |
21 (91.3%) |
9 (100%) |
12 (85.7%) |
|
Ibrutinib progression and prior venetoclax |
13 (56.5%) |
5 (55.6%) |
8 (57.1%) |
Methods
- After three days of lymphodepleting chemotherapy, patients received liso-cel infusion at either dose level 1 or 2 (one: 50 x 10 6; two: 100 x 10 6)
- Patients monitored for dose-limiting toxicities
- Minimal residual disease (MRD) was assessed using flow cytometry in blood, and through next-generation sequencing in bone marrow
Key findings
- 16 patients received liso-cel (n = 6 in dose level one, and n = 10 in dose level two)
- One dose-limiting toxicity, grade four hypertension at dose level 2
- The most common adverse events (AEs) were cytopenias:
- Thrombocytopenia, 75%
- Anemia, 69%
- Neutropenia, 63%
- Leukopenia, 56%
- One patient had grade 3 cytokine release syndrome (CRS), three patients had grade 3 neurological events
- 83% of patients with complete response (CR) at 6 months remained in CR
- Durable objective responses (67%) and undetectable MRD (64%) maintained at 6 months
Conclusion
Dr Siddiqi mentioned how toxicities related to liso-cell were manageable, with promising clinical activity in patients who had been heavily pre-treated with ibrutinib and venetoclax. At both dose levels, adverse events were manageable, with a follow-up of 9 months showing a high proportion of durable responses that improved over time. The majority of responses and undetected MRD were achieved by day 30, with a large proportion of patients remaining in CR at 6 months, remaining in CR.
A phase II study is currently enrolling patients at dose level 2, stemming from the results of this phase I trial. Patients in this trial will be treated with liso-cel in combination with ibrutinib.