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EHA 2019 | Investigating liso-cel in R/R chronic lymphocytic leukemia and small lymphocytic lymphoma

Jun 27, 2019

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.

Expert Opinion

  1. Siddiqi, T. et al. TRANSCEND CLL 004: Minimal residual disease negative response after lisocabtagene maraleucel (liso-cel) in patients with relapsed/refractory chronic lymphocytic leukemia or small lymphocytic lymphoma. Abstract S109. 24 thEuropean Hematology Association Congress, Amsterdam, NL. 2019 Jun 14.