Analysis Identifies Pre-Treatment Factors Associated With Liso-Cel Response in CLL

The phase I/II TRANSCEND CLL 004 study evaluated lisocabtagene maraleucel (liso-cel) monotherapy for relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). An exploratory analysis of initial findings from the study pinpointed patient pre-treatment characteristics associated with response. They were presented at the Society of Hematologic Oncology 2024 Annual Meeting in Houston, Texas.

In this analysis, having a “lower baseline disease burden (lower [sum of the product of perpendicular diameters (SPD)], lower [beta-2 microglobulin (B2M)], bulky disease absence) was correlated with increased likelihood of achieving response,” wrote lead investigator William G. Wierda, MD, PhD, of the University of Texas MD Anderson Cancer Center in Houston.

The exploratory analysis involved post hoc univariable analyses of data from 87 TRANSCEND CLL 004 patients. The patients had a median follow-up of 21.1 months.

The investigators found that patients who achieved complete response (CR) had a lower median pre-lymphodepleting chemotherapy (pre-LDC) B2M level than patients who did not, at 3.3 mg/L versus 4.7 mg/L, respectively. Also associated with CR attainment was lower CLL screening Rai stage: 29.7% of patients with stage 0 through II disease attained CR versus 11.4% of patients with stage III through IV disease. The investigators also noted that patients with CR had a lower median pre-LDC lymph node SPD as compared with those without CR, at 24.8 cm² versus 40.9 cm², respectively.

Regarding pre-LDC characteristics that correlated with overall response (OR), patients without bulky disease had an OR rate of 63.2% versus 31.7% in patients with bulky disease. Patients who achieved OR had a lower median SPD, at 25.0 cm² versus 59.3 cm². Finally, lower BALL risk scores were linked to higher OR rates; OR was achieved in 61.3% of patients with scores of 0 through 1 versus in 18.2% of patients with a score of 4.

Dr. Wierda wrote that liso-cel was found to be effective regardless of high-risk CLL features, and “there was no correlation between response and screening age, sex, mutated TP53, 17p deletion, mutated TP53 and 17p deletion, unmutated immunoglobulin heavy-chain variable region, or complex karyotype.”

Reference

Wierda WG, Maloney DG, Kenderian SS, et al. Characteristics associated with response to lisocabtagene maraleucel (liso-cel) in patients with R/R CLL/SLL: exploratory analyses from the phase 1/2 TRANSCEND CLL 004 study. Abstract #CLL-184. Presented at the Society of Hematologic Oncology 2024 Annual Meeting; September 4-7, 2024; Houston, Texas.