外周 CAR-T 细胞 (CAR-T 细胞) mRNA 表达水平与弥漫大 B 细胞淋巴瘤患者毒性和结局的相关性

Cytokine-release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) are significant complications in patients with relapsed/refractory diffuse large B-cell lymphoma undergoing chimeric antigen receptor T-cell (CAR-T cell) therapy.

However, it remains unclear whether CAR-T cell expression itself is clinically relevant.

We assessed CAR-T cell mRNA expression and DNA concentration by digital droplet PCR in peripheral blood from 14 sequential CAR-T cell recipients. Patients were grouped according to CAR-T cell peak expression. Patients with high CAR-T cell peak expression (8 patients; 57%) had higher rates of ICANS (p=0.

0308) and intensive care unit admission (p=0. 0404), longer durations of hospitalization (p=0. 0077), and, although not statistically significant, a higher rate of CRS (p=0. 0778). There was a correlation of CAR-T cell mRNA expression with DNA concentration, but CAR-T cell expression levels failed to correlate to response or survival.

Our data suggest that higher CAR-T cell peak mRNA expression is associated with increased risk for ICANS and possibly CRS, requiring further investigation in larger studies. Sitokin sal m sendromu (CRS) ve imm n efekt r h cre ile ili kili n rotoksisite sendromu (ICANS), kimerik antijen resept r T-h cresi (CAR-T h cresi) tedavisi g ren n ksetmi /refrakter diff z b y k B-h creli lenfoma hastalar nda nemli komplikasyonlard r. Bununla birlikte, CAR-T h cre ifadesinin klinikle ili kili olup olmad belirsizli ini korumaktad r. Ond rt CAR-T h cre al c s ndan periferik kanda dijital damlac k PCR ile CAR-T h cresi mRNA ekspresyonunu ve DNA konsantrasyonunu de erlendirdik.

Hastalar, CAR-T h cre pik ifadesine g re grupland r ld . Y ksek CAR-T h cre pik ekspresyonu olan hastalar (8 hasta; %57) daha y ksek ICANS (p=0,0308) ve yo un bak ma yat (p=0,0404), daha uzun hastanede yat s releri (p=0,0077) ve istatistiksel olarak anlaml olmasa da, daha y ksek CRS oran na sahipti (p=0,0778).

CAR-T h cresi mRNA ekspresyonu ile DNA konsantrasyonu aras nda bir korelasyon vard , ancak CAR-T h cresi ekspresyon seviyeleri, yan t veya hayatta kalma ile korelasyon g stermedi. Verilerimiz, daha y ksek CAR-T h cre zirvesi mRNA ekspresyonunun, daha b y k al malarda daha fazla ara t rmay gerektiren, artan ICANS ve muhtemelen CRS riski ile ili kili oldu unu g stermektedir.