CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Don't Put the CART Before the Horse: The Role of Radiation Therapy in Peri-CAR T-cell Therapy for Aggressive B-cell Non-Hodgkin Lymphoma.
Don't Put the CART Before the Horse: The Role of Radiation Therapy in Peri-CAR T-cell Therapy for Aggressive B-cell Non-Hodgkin Lymphoma.
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BRT 后接 CAR-T 似乎与 r/r bNHL 中相比 SRT 改善的 LC 相关。尽管如此,如果全面实施,SRT 为 CAR-T 后复发的局限性(<5 个部位)疾病提供了一种有前景的挽救干预。
对于复发/难治性(r/r)B细胞非霍奇金淋巴瘤(bNHL),将放射治疗(RT)与嵌合抗原受体(CAR)T细胞疗法(CAR-T)相结合的最佳方法仍不明确。本研究记录了在接受CAR-T 前接受桥接放射治疗(BRT)的患者中的RT局部控制率,并将其与在接受CAR-T 后接受挽救性放射治疗(SRT)的患者进行比较。本文进一步报告了一种将SRT用于CAR-T 后疾病的有前景的方法,并确定了RT野内复发的预测因素。
我们回顾性分析了2018年至2021年间接受CAR-T 和RT的83例r/r bNHL患者,其中35例在CAR-T 输注前接受BRT,48例在CAR-T 输注后接受SRT。RT被定义为全面性(compRT;即治疗所有活动性疾病部位)或局灶性(focRT)。局限性疾病被定义为适合compRT、涉及<5个活动性疾病部位。
在RT时,与CAR-T 后接受SRT的患者相比,CAR-T 前接受BRT的患者疾病部位更大(中位直径,8.7 vs 5.5 cm;P = .01),并且接受的剂量显著更低(中位等效2-Gy剂量,23.3 vs 34.5 Gy;P = .002)。在共识别出的124个照射部位中,59个桥接部位中有8个(13%)和65个挽救部位中有21个(32%)发生了野内复发,分别对应1年局部控制(LC)率为84%和62%(P = .009)。与接受focSRT的局限性疾病患者(n = 11)相比,接受compSRT的CAR-T 后局限性疾病患者(n = 37,其中n = 26接受compSRT)具有更好的总生存期(51% vs 12%;P = .028)、后续进展自由(31% vs 0%;P < .001)和后续事件自由(19% vs 0%;P = .011)。
The optimal approach to incorporate radiation therapy (RT) in conjunction with chimeric antigen receptor (CAR) T-cell therapy (CART) for relapsed/refractory (r/r) B-cell non-Hodgkin lymphoma (bNHL) remains unclear. This study documented the RT local control rate among patients who received bridging radiation therapy (BRT) before CART and compares it with those who received salvage radiation therapy (SRT) after CART. This article further reports on a promising way to use SRT for post-CART disease and identifies predictors for RT in-field recurrence. METHODS AND MATERIALS: We retrospectively reviewed 83 patients with r/r bNHL who received CART and RT, either as BRT pre-CART infusion (n = 35) or as SRT post-CART infusion (n = 48), between 2018 and 2021. RT was defined as comprehensive (compRT; ie, treated all sites of active disease) or focal (focRT). Limited disease was defined as disease amenable to compRT, involving <5 active disease sites.
At time of RT, patients who received BRT before CART had bulkier disease sites (median diameter, 8.7 vs 5.5 cm; P = .01) and were treated to significantly lower doses (median equivalent 2-Gy dose, 23.3 vs 34.5 Gy; P = .002), compared with SRT post-CART. Among 124 total irradiated sites identified, 8 of 59 (13%) bridged sites and 21 of 65 (32%) salvaged sites experienced in-field recurrence, translating to 1-year local control rates (LC) of 84% and 62%, respectively (P = .009). Patients with limited post-CART disease (n = 37) who received compSRT (n = 26) had better overall survival (51% vs 12%; P = .028), freedom from subsequent progression (31% vs 0%; P < .001), and freedom from subsequent event (19% vs 0%; P = .011) compared with patients with limited disease who received focSRT (n = 11).
BRT followed by CART appears to be associated with improved LC compared with SRT in r/r bNHL. Nonetheless, SRT offers a promising salvage intervention for limited (<5 sites) relapsed post-CART disease if given comprehensively.
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