A higher absolute lymphocyte count (ALC) after receipt of chimeric antigen receptor (CAR) T-cell therapy may be associated with improved progression-free and/or overall survival in patients with non-Hodgkin lymphoma, according to findings from the 2025 American Society of Hematology (ASH) Annual Meeting (Abstract 5506).
“If we see that a patient has low ALC and might relapse, we can try another strategy. Finding a kinetic marker that doesn’t take a lot of resources to check but could still make a real difference in a patient’s course of treatment is exciting,” said first author Helen Gandler, MD, a third-year resident in Internal Medicine at Temple Hospital, who was mentored by senior study author Anthony Stack, DO, Assistant Professor in the Blood Cancer and Cellular Therapy Institute at Fox Chase Cancer Center.
Background and Study Methods
Preliminary research has shown that lymphocyte kinetics—including ALC, the ratio of absolute lymphocyte/monocyte count, and lymphocyte area under the curve—are indicators of immune status that can provide prognostic value in CAR T-cell therapy.
Researchers conducted a single-center, retrospective study that explored the association between ALC kinetics and clinical outcomes for 45 patients with non-Hodgkin lymphoma who were treated with the CAR T-cell therapy axicabtagene ciloleucel between October 2018 and November 2023.
Key Findings
The overall median progression-free survival was 19.1 months and the overall survival was 22.1 months. Cytokine-release syndrome was observed in 71% of patients and immune effector cell–associated neurotoxicity syndrome was reported in 31%.
The median ALC at the time of leukapheresis was 0.6 x 109 cells/L (range = 0.1–2.5 x 109 cells/L) and 0.1 x 109 cells/L (range = 0–0.7 x 109 cells/L) at the time of CAR T-cell infusion. The ratio of absolute lymphocyte/monocyte count at leukapheresis had a median of 1.0 (range = 0.2–9.0). Peak ALC occurred after a median of 10 days and the median peak value was 0.7 x 109 cells/L (range = 0.2–7 x 109 cells/L). The median rate of ALC expansion was 0.04 x 109 cells*day/L (range = 0-0.12 x 109 cells*day/L).
In the first 15 days after infusion of CAR T-cell therapy, the median area under the curve for ALC was 3.2 x 109 cells*day/L (range = 0.6-11.6 x 109 cells*day/L).
Patients who had a higher ALC than the median at leukapheresis had a significantly prolonged progression-free survival compared with those with a median count after CAR T-cell therapy (not reached vs 10.1 months; P = .0179) and overall survival (not reached vs 34.0 months; P = .0439). Those with an above-the-median 10-day rate of ALC expansion had a greater complete response rate than those with median expansion (87% vs 59%; P = .0472) and a prolonged progression-free survival (not reached vs 34.5 months; P = .0242).
The rate to peak ALC expansion above the median was also associated with a prolonged progression-free survival (not reached vs 9.2 months; P = .0487). A less-than-10-day time to peak ALC was associated with a prolonged progression-free (not reached vs 8.4 months) and overall survival (not reached vs 20.75 months) compared with those with a longer time for the ALC to peak.
A significantly prolonged progression-free survival (not reached vs 8.2 months; P = .0028), and overall survival (not reached vs 20.8 months; P = .0031), was also experienced by patients who had a peak ALC above the median within 30 days of their CAR T-cell infusion.
“It makes sense that patients showing robust immune responses are the ones having better progression-free survival and overall survival,” said Dr. Gandler.
A higher median area under the curve for ALC for the first 15 days after CAR T-cell infusion was associated with a longer progression-free survival (not reached vs 10.1 months; P = .0561), although it was not significant, and a prolonged overall survival (not reached vs 34.0 months; P = .0387), that was significant. The absolute lymphocyte/monocyte counts at the time of leukapheresis, on the other hand, was not associated with response rate or survival.
The researchers intend to further study the association, including in patients treated with lisocabtagene maraleucel.
Disclosure: For full disclosures of the study authors, visit ashpublications.org.
