New Data on CLL Therapies Presented at the 2025 ASCO Annual Meeting

Photo Credit: iStock.com/Nemes Laszlo

The 2025 ASCO Annual Meeting showcased new data on therapies for chronic lymphocytic leukemia, including zanubrutinib, acalabrutinib, and liso-cel.

New abstracts presented at the 2025 ASCO Annual Meeting highlight the latest strategies in treating chronic lymphocytic leukemia (CLL), including:

• The CAR‑T therapy lisocabtagene maraleucel versus standard care in heavily pre‑treated disease.
• A real‑world comparison of the Bruton tyrosine‑kinase inhibitors (BTKi) zanubrutinib and acalabrutinib in the frontline setting.

Liso-cel Versus Standard of Care

Patients with relapsed or refractory (R/R) CLL/small‑cell lymphoma (SLL) who have failed both a BTKi and venetoclax face few therapeutic options and poor outcomes. To help address gaps, William G. Wierda, MD, PhD, and colleagues compared the benefit of lisocabtagene maraleucel (liso‑cel) with standard of care.

The researchers compared 66 patients receiving liso-cel with 212 matched SOC patients. The patients were selected from the Flatiron, COTA, and ConcertAI databases, and treatment spanned from 1993 to 2023. All patients were at least 18 years old, had received two or more prior lines of therapy (including a BTKi and venetoclax), and had initiated subsequent treatment for CLL/SLL.

Using inverse‑probability‑of‑treatment weighting and multivariable regression, the researchers balanced prognostic variables such as age, sex, race, time since diagnosis, Rai stage, bulky disease, ECOG performance status, high‑risk cytogenetics, prior chemoimmunotherapy or PI3K inhibitor exposure, and refractoriness to BTKi and venetoclax.

Median follow‑up was 35.4 months for liso‑cel and 17.2 months for SOC. After adjustment, the overall response rate reached 52.5% (95% CI, 34.8–79.2) with liso‑cel versus 19.2 % (95% CI, 14.1–26.1) with SOC.

Median progression‑free survival (PFS) was 12.0 months (95% CI, 10.8–13.2) for liso‑cel and 4.4 months (95% CI, 3.2–5.5) for SOC, yielding a hazard ratio of 0.40 (95% CI, 0.24–0.68). PFS probabilities at 24 and 36 months were 46.3% and 30.3% with liso‑cel compared with 11.5% and 5.1% for SOC.

Median overall survival (OS) almost doubled, measuring 33.6 months (95% CI, 31.7–35.5) for liso‑cel versus 14.8 months (95% CI, 9.4–20.1) for SOC; the corresponding hazard ratio was 0.47 (95% CI, 0.28–0.79). Two- and three‑year OS probabilities were 73.4% and 42.6% for liso‑cel versus 35.1% and 29.7% for SOC.

The researchers concluded that liso‑cel significantly benefited patients with R/R disease who had already received two prior lines of therapy.

Zanubrutinib Versus Acalabrutinib

Next‑generation BTKis have broadened options for first‑line CLL/SLL, yet head‑to‑head evidence remains limited. Jing-Zhou Hou, MD, PhD, and colleagues sought to examine the comparative effectiveness of zanubrutinib versus acalabrutinib in routine clinical practice.

Using the Integra Connect PrecisionQ de‑identified database, the researchers identified US adults who began BTKi monotherapy from January 2020 to November 2023. The patients were followed through July 3, 2024. Each of the 200 patients who received zanubrutinib was matched 1:2, by age and sex, to 400 patients who received acalabrutinib. Among both cohorts, the median age was 75 years (IQR, 67–81), and 36.5% of patients were female.

Baseline performance status was comparable between groups, with ECOG 0–1 recorded in 87.5% of zanubrutinib and 87.8% of acalabrutinib recipients. The median follow-up was 11.0 months (range, 2.3–32.2) for zanubrutinib and 15.9 months (range, 0.9–53.3) for acalabrutinib.

Kaplan–Meier analysis showed higher probabilities of remaining on initial therapy and of avoiding escalation to a subsequent line of treatment with zanubrutinib at every landmark.

At 12 months, 80.6% of zanubrutinib recipients versus 66.6% of acalabrutinib recipients were still receiving their index BTKi. In addition, 84.6% of patients receiving zanubrutinib had not advanced to a next line of therapy, compared with 80.5% of those receiving acalabrutinib. The 24‑month estimates demonstrated the same directional benefit for zanubrutinib: ongoing therapy rates of 75.9% versus 52.8%, and no subsequent therapy rates of 71.7% versus 66.5%.

Median overall survival was not reached for either cohort.

The researchers concluded that patients on zanubritinib were significantly more likely to remain on treatment and less likely to require another line of therapy compared with patients receiving acalabrutinib.