KEY TAKEAWAYS
- The phase 1/2 TRANSCEND CLL 004 study evaluated liso-cel in patients with R/R CLL/SLL.
- Primary endpoint: CR/CRi rate by IRC in efficacy-evaluable pts with prior therapy at DL2; Secondary endpoints: ORR and uMRD.
- Liso-cel confirmed durable CR/CRi, high uMRD rates, and a manageable safety profile in patients with heavily pretreated, high-risk R/R CLL/SLL and high unmet needs.
The phase 1/2, single-arm, multicenter study evaluated the use of lisocabtagene maraleucel (liso-cel) in relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL)/small lymphocytic leukemia (SLL). In the trial, liso-cel was given at a target dose of either 50 (DL1) or 100 (DL2) × 106 CAR+ T cells to patients who had received at least two prior lines of therapy, including a BTKi. The primary endpoint was the rate of CR and CR with incomplete marrow recovery (CRi) by IRC according to the 2018 iwCLL criteria. The analysis was conducted on a subset of efficacy-evaluable pts who had disease progression on BTKi and ven failure (primary efficacy analysis set [PEAS]) at DL2 (null hypothesis [H0]: ≤5%). The study examined ORR (H0: ≤40%) and rate of undetectable minimal residual disease (uMRD; 10−4) in the blood (H0: ≤5%) as secondary keypoints.
Of 137 leukapheresed patients (pts), 117 were given liso-cel (safety set), 96 (DL1 = 9; DL2 = 87) were efficacy evaluable, and 53 (DL1 = 4; DL2 = 49) were in the PEAS. In the safety set, the median (range) age was 65 y (49–82), 83% of pts had high-risk features, the median (range) lines of prior therapy were (2–12), and all pts had prior BTKi. The median on-study follow-up for the safety set was 21.1 mo (0.4–55.6). The PEAS at DL2 showed a CR/CRi rate of 18.4%, meeting the primary endpoint (95% CI, 8.8–32.0; 1-sided p = 0.0006). The ORR was 42.9%, but it was not statistically significant (95% CI, 28.8–57.8; 1-sided p = 0.3931). The uMRD rate demonstrated an exceptional outcome, with 63.3% in blood and 59.2% in the marrow. The median (95% CI) DOR exhibited an impressive figure of 35.3 months (11.01–not reached [NR]) with a median follow-up of 19.7 months. The median duration of CR/CRi was NR. In the study’s safety set, the rate of any-grade CRS was 84.6% (gr 3, 8.5%; no gr 4/5), and neurological events (NE) was 45.3% (gr 3, 17.9%; gr 4, 0.9%; no gr 5). Around 69.2% pts received tocilizumab and/or corticosteroids to manage CRS/NEs. The rate of grade ≥3 infections was 17.1%, hypogammaglobulinemia occurred in 15.4%, and prolonged cytopenia in 53.8% of cases. One death related to liso-cel attributed to hemophagocytic lymphohistiocytosis was reported. Liso-cel expanded at an alarming rate and remained detectable by qPCR in blood up to 36 mo after infusion.
Liso-cel showed durable CR/CRi, high uMRD rates, and a manageable safety profile in heavily pretreated, high-risk R/R CLL/SLL pts with high unmet needs.
Source: https://onlinelibrary.wiley.com/doi/10.1002/hon.3163_26
Clinical Trial: https://classic.clinicaltrials.gov/ct2/show/NCT03331198
Siddiqi, T., Maloney, D. G., Kenderian, S. S., Brander, D. M., Dorritie, K., Soumerai, J., Riedell, P. A., Shah, N. N., Nath, R., Fakhri, B., Stephens, D. M., Ma, S., Feldman, T., Solomon, S. R., Schuster, S. J., Perna, S. K., Tuazon, S., Ou, S., Papp, E., Wierda, W. LISOCABTAGENE MARALEUCEL (LISO-CEL) IN R/R CHRONIC LYMPHOCYTIC LEUKEMIA (CLL)/SMALL LYMPHOCYTIC LYMPHOMA (SLL): PRIMARY ANALYSIS OF TRANSCEND CLL 004. Hematological Oncology, 41, 60-62. https://doi.org/10.1002/hon.3163_26
