Comparison of outcomes for patients (pts) with R/R chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) previously treated with Bruton tyrosine kinase inhibitor (BTKi) and venetoclax from the TRANSCEND CLL 004 study versus a matched cohort of real-world (RW) pts.

Abstract

7039 Background: Pts with R/R CLL/SLL who failed BTKi and venetoclax have limited treatment (tx) options and poor prognoses. FDA approval of lisocabtagene maraleucel (liso-cel) for R/R CLL/SLL was based on positive results from TRANSCEND CLL 004 (NCT03331198), a single-arm trial. We assessed relative efficacy of liso-cel vs standard of care (SOC) by identifying (or assembling) an external comparator cohort of pts treated in a RW setting. Methods: Pts from TRANSCEND CLL 004 and a matched RW cohort were analyzed. Eligible pts were ≥ 18 y with CLL/SLL, had ≥ 2 prior lines of therapy (pLoT), including a BTKi and venetoclax, and started subsequent tx for CLL/SLL. SOC pts were selected from de-identified datasets (Flatiron [1993–2023], COTA [2000–2023], and ConcertAI [1997–2022]). TRANSCEND CLL 004 eligibility criteria were applied as applicable. Liso-cel pts were eligible trial participants treated with liso-cel and efficacy-evaluable. Endpoints were ORR, PFS, and OS. Inverse probability of tx weighting (IPTW) and regression model were used to balance pt characteristics between cohorts, including age, sex, race, time from initial diagnosis, Rai stage, bulky disease, ECOG PS, high-risk cytogenetics, pLOT, prior chemoimmunotherapy and phosphatidylinositol 3-kinase inhibitor (PI3Ki), and refractoriness to BTKi and venetoclax. Results: Analysis included 278 pts (SOC, n = 212; liso-cel, n = 66). SOC regimens included chemotherapy, immunotherapy (excluding CAR T cell therapy), BTKi, venetoclax, PI3Ki, and combinations. Median follow-up was 17.2 mo for SOC and 35.4 mo for liso-cel. Most pt characteristics were balanced after IPTW (Table) with imbalance adjusted by regression. After adjustment, ORR (95% CI) was 19.2% (14.1–26.1) for SOC vs 52.5% (34.8–79.2) for liso-cel. Median (95% CI) PFS was 4.4 mo (3.2–5.5) for SOC vs 12.0 mo (10.8–13.2) for liso-cel (HR, 0.40; 95% CI, 0.24–0.68). PFS probabilities at 24 and 36 mo were 11.5% and 5.1% for SOC vs 46.3% and 30.3% for liso-cel. Median (95% CI) OS was 14.8 mo (9.4–20.1) for SOC vs 33.6 mo (31.7–35.5) for liso-cel (HR, 0.47; 95% CI, 0.28–0.79). OS probabilities at 24 and 36 mo were 35.1% and 29.7% for SOC vs 73.4% and 42.6% for liso-cel. Conclusions: Liso-cel was associated with significantly improved response, delayed progression, and prolonged survival vs SOC in pts with R/R CLL/SLL after ≥ 2 pLOTs, including a BTKi and venetoclax. Clinical trial information: NCT03331198 . Characteristics before/after IPTW. SOC (before) Liso-cel (before) SOC (after) Liso-cel (after) Mean age, y 70.5 65.4 68.7 69.3 Rai stage III/IV, % 56 57 55 52 Bulky disease, % 86 62 77 69 High-risk cytogenetics, % 83 83 84 76 Mean pLOTs 3.9 6.1 4.5 4.6 Prior chemoimmunotherapy, % 58 88 67 72 Prior PI3Ki, % 18 30 22 23 BTKi refractory, % 69 88 74 77 Venetoclax refractory, % 54 92 64 84