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ICML 2021 | TRANSCEND-CLL-004: liso-cel in CLL

William Wierda, MD, PhD, University of Texas MD Anderson Cancer Center, Houston, TX, provides an overview of the Phase I/II TRANSCEND-CLL-004 trial (NCT03331198), which investigated the safety and efficacy of lisocabtagene maraleucel in patients with relapsed or refractory chronic lymphocytic leukemia (CLL). In one cohort of 23 patients who additionally received ibrutinib with lisocabtagene maraleucel, a majority of patients achieved complete remission (CR) and undetectable minimal residue disease (MRD) in blood. The safety profile was also favorable, with no cases of grade 3 cytokine release syndrome reported and a few cases of manageable neurotoxicity events. This interview took place during the 2021 International Conference on Malignant Lymphoma (16-ICML).

Transcript (edited for clarity)

TRANSCEND-CLL-004 is a clinical trial of CD19 CAR T-cell therapy for patients with relapsed and refractory chronic lymphocytic leukemia with the Juno BMS liso-cel product, and trial data has been presented at prior meetings.

Thus far, there have been two cohorts of patients treated on this trial, a monotherapy cohort, and Tanya Siddiqi has presented a couple of times the updated data for that cohort...

TRANSCEND-CLL-004 is a clinical trial of CD19 CAR T-cell therapy for patients with relapsed and refractory chronic lymphocytic leukemia with the Juno BMS liso-cel product, and trial data has been presented at prior meetings.

Thus far, there have been two cohorts of patients treated on this trial, a monotherapy cohort, and Tanya Siddiqi has presented a couple of times the updated data for that cohort. Then there is a combination cohort with ibrutinib patients. There’s preclinical data, and data from other sites, individual sites who have done CAR T-cell work and suggesting that there’s a better product that’s generated or more potent product when the T cells are harvested for production from patients who are on ibrutinib versus those who are not. Then there’s also some data that they may be more effective when given in the setting of concurrent ibrutinib, and the toxicities may be better.

So there’s a second cohort that was added with ibrutinib plus liso-cel, and that’s what I have reported at ICML this June. That cohort was previously reported at ASH. At the ASH presentation, there were 19 patients enrolled. Now there are 23 patients enrolled in that cohort, and the updated data reports the safety and tolerability of liso-cel plus ibrutinib in this cohort. There were four patients treated at the lower dose level and 19 patients treated at dose level two, which is a hundred million cells. That’s the dose that’s moving forward with further expansion is the dose level two. We saw and reported complete remission in about 60% of the patients treated, and the MRD undetectable rate was nearly 90%. It was 86%, I believe, for patients treated in this cohort.

Safety was very good. The incidents of grade III or greater cytokine release was low, less than 5%. Actually in the 19 patients who were treated in the dose level two cohort, we didn’t see any grade III or greater cytokine release syndrome. Neurotoxicity is a little bit more common, and we did report a neurotoxicity, including grade III or greater in 21% of the patients treated in dose level two. But those were manageable, and we managed them with our standard approaches of steroids and/or tocilizumab depending on the clinical setting.

So an updated data, very active, very durable responses that we’re seeing with the relatively short follow-up we have. But the median duration of response and progression-free survival, the median has not yet been reached, and so we continue enrollment and follow up on this study. We’re excited about the prospect and advances that cellular therapy poses for patients with CLL, particularly relapsed and refractory. I should mention also that there were a number of patients with refractory disease, or patients who were refractory to BTK inhibitor and/or BCL2 inhibitor, who responded on this study.

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