TY - JOUR
T1 - Impact of conditioning chemotherapy on lymphocyte kinetics and outcomes in LBCL patients treated with CAR T-cell therapy
AU - Strati, Paolo
AU - Jallouk, Andrew P.
AU - Sun, Ryan
AU - Choi, Jaihee
AU - Das, Kaberi
AU - Cherng, Hua Jay
AU - Ahmed, Sairah
AU - Lee, Hun J.
AU - Iyer, Swaminathan P.
AU - Nair, Ranjit
AU - Nastoupil, Loretta J.
AU - Steiner, Raphael E.
AU - Huff, Chad D.
AU - Yu, Yao
AU - Mistry, Haleigh
AU - Pulsifer, Brittany
AU - Noorani, Mansoor
AU - Saini, Neeraj
AU - Shpall, Elizabeth J.
AU - Kebriaei, Partow
AU - Flowers, Christopher R.
AU - Westin, Jason R.
AU - Hildebrandt, Michelle A.T.
AU - Neelapu, Sattva S.
N1 - Publisher Copyright:
© 2022, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2022/11
Y1 - 2022/11
N2 - Conditioning chemotherapy (CCT) has been shown to be essential for optimal efficacy of chimeric antigen receptor (CAR) T-cell therapy. Here, we determined whether the change in absolute lymphocyte count, referred to as delta lymphocyte index (DLIx), may serve as a surrogate marker for pharmacodynamic effects of CCT and whether it associated with germline genetic variants in patients with large B-cell lymphoma (LBCL). One-hundred and seventy-one patients were included, of which 86 (50%) received bridging therapy post-leukapheresis. Median DLIx was 0.5 × 109/L (range, 0.01–2.75 × 109/L) and was significantly higher in patients who achieved complete response (p = 0.04). On multivariate analysis, low DLIx was associated only with use of bridging therapy (odds ratio 0.4, 95% CI 0.2–0.8, p = 0.007). Low DLIx was independently associated with shorter progression-free (p = 0.02) and overall survival (p = 0.02). DLIx was associated with genetic variations related to drug metabolism and macrophage biology such as ABCB1, MISP and CPVL. The impact of CCT on lymphocyte count is affected by use of bridging therapy but change in lymphocyte count is independently associated with efficacy. Studies aimed at investigating macrophage biology in this setting may suggest strategies to increase the efficacy of CCT and improve outcomes.
AB - Conditioning chemotherapy (CCT) has been shown to be essential for optimal efficacy of chimeric antigen receptor (CAR) T-cell therapy. Here, we determined whether the change in absolute lymphocyte count, referred to as delta lymphocyte index (DLIx), may serve as a surrogate marker for pharmacodynamic effects of CCT and whether it associated with germline genetic variants in patients with large B-cell lymphoma (LBCL). One-hundred and seventy-one patients were included, of which 86 (50%) received bridging therapy post-leukapheresis. Median DLIx was 0.5 × 109/L (range, 0.01–2.75 × 109/L) and was significantly higher in patients who achieved complete response (p = 0.04). On multivariate analysis, low DLIx was associated only with use of bridging therapy (odds ratio 0.4, 95% CI 0.2–0.8, p = 0.007). Low DLIx was independently associated with shorter progression-free (p = 0.02) and overall survival (p = 0.02). DLIx was associated with genetic variations related to drug metabolism and macrophage biology such as ABCB1, MISP and CPVL. The impact of CCT on lymphocyte count is affected by use of bridging therapy but change in lymphocyte count is independently associated with efficacy. Studies aimed at investigating macrophage biology in this setting may suggest strategies to increase the efficacy of CCT and improve outcomes.
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U2 - 10.1038/s41375-022-01704-z
DO - 10.1038/s41375-022-01704-z
M3 - Article
C2 - 36127509
AN - SCOPUS:85138332501
SN - 0887-6924
VL - 36
SP - 2669
EP - 2677
JO - Leukemia
JF - Leukemia
IS - 11
ER -