Lisocabtagene Maraleucel in High-Risk and Pretreated Patients with Relapsed or Refractory CLL

Lisocabtagene maraleucel (liso-cel) is an investigational, chimeric antigen receptor T-cell therapy designed to target CD19 on B-cells. In the ongoing TRANSCEND CLL 004 study, liso-cel is under investigation in patients with relapsed or refractory chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). Researchers reported outcomes of patients in the phase 1 monotherapy cohort after a median follow-up of 18 months.

The ongoing, phase 1/2, multicenter, TRANCEND CLL 004 trial includes adult patients with relapsed or refractory CLL or SLL. In the reported cohort, eligible patients with standard-risk disease had received 3 or more lines of prior therapy. Patients with high-risk disease, including 17p deletion, TP53 mutation, unmutated IGHV, or complex karyotype, had received 2 or more lines of prior therapy.¹

After 3 days of lymphodepletion, patients received liso-cel infusion. Dose-limiting toxicities were evaluated 28 days post-infusion. Responses and minimal residual disease (MRD) were assessed. Persistence of liso-cel was monitored by quantitative polymerase chain reaction.

Overall, 23 patients were evaluable for safety and 22 patients were evaluable for efficacy. Participants had a median age of 66 years. Patients had received a median of 6 prior therapies and 83% of patients had high-risk disease. All patients had received prior treatment with Imbruvica (ibrutinib), and 91% were refractory to or had relapsed on Imbruvica. The remaining 9% of patients were intolerant to Imbruvica. Overall, 48% were refractory to both a prior Bruton tyrosine kinase (BTK) inhibitor and Venclexta (venetoclax).

Of the 22 patients evaluable for efficacy, the overall response rate was 92%. By day 30, 68% of patients achieved an overall response. At 15- and 18-month post-infusion, 53% and 50% of patients maintained their responses, respectively. At median follow-up of 18 months, the median duration of response was not reached in patients who had achieved a response to liso-cel. The median progression-free survival was 18 months in all patients evaluable for efficacy. In patients with disease refractory to both a prior BTK inhibitor and Venclexta, the overall response rate was similar to that of the total evaluable population, with a complete response rate of 60%.

Of 20 MRD-evaluable patients, 15 had undetectable MRD (uMRD) in the blood, and of these, 13 had uMRD in the bone marrow. By day 30, 60% of patients had achieved uMRD in the bone marrow. Preliminary data demonstrate that in 36% of patients, liso-cel was detectable in the blood for up to 18 months following infusion.

Researchers conclude that in this cohort of heavily pretreated, high-risk patients with relapsed or refractory CLL, treatment with liso-cel resulted in a high rate of uMRD. This was true for patients with disease refractory to both a BTK inhibitor and Venclexta as well. Reponses to liso-cel treatment were rapid and durable, with liso-cel detectable in the blood for up to 18 months post-infusion. In this longer follow-up, no late or delayed adverse events of concern emerged. The phase 2 monotherapy expansion of the TRANSCEND CLL 004 study is currently enrolling.

---

Reference

1. Siddiqi T, Soumerai JD, Dorritie KA, et al. Updated Follow-up of Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma Treated with Lisocabtagene Maraleucel in the Phase 1 Monotherapy Cohort of Transcend CLL 004, Including High-Risk and Ibrutinib-Treated Patients. American Society of Hematology 62nd Annual Meeting and Exposition. Abstract 546.