不要本末倒置:放疗在 CAR-T 细胞治疗侵袭性 B 细胞非霍奇金淋巴瘤中的作用。
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.
机构信息
Department of Radiation Oncology, Mayo Clinic, Jacksonville, Florida.
Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota.
出版信息
Int J Radiat Oncol Biol Phys. 2023 Aug 1;116(5):999-1007. doi: 10.1016/j.ijrobp.2022.12.017. Epub 2022 Dec 21.
PURPOSE
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.
RESULTS
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).
CONCLUSIONS
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.
目的
对于复发/难治性(r/r)B 细胞非霍奇金淋巴瘤(bNHL)患者,联合嵌合抗原受体(CAR)T 细胞疗法(CART)时,最佳的放疗(RT)方法仍不清楚。本研究记录了在 CART 前接受桥接放疗(BRT)的患者的 RT 局部控制率,并将其与在 CART 后接受挽救性放疗(SRT)的患者进行了比较。本文进一步报告了一种有前途的使用 SRT 治疗 CART 后疾病的方法,并确定了 RT 局部复发的预测因素。
方法和材料
我们回顾性分析了 2018 年至 2021 年间 83 例接受 CART 和 RT 的 r/r bNHL 患者,这些患者在 CART 前接受了 BRT(n=35)或在 CART 后接受了 SRT(n=48)。RT 定义为全面性(compRT;即,治疗所有活跃疾病部位)或局灶性(focRT)。局限性疾病定义为可接受 compRT 的疾病,涉及<5 个活跃疾病部位。
结果
在接受 RT 时,与 SRT 后相比,在 CART 前接受 BRT 的患者疾病部位更大(中位直径,8.7 对 5.5cm;P=0.01),并且接受的剂量明显更低(中位等效 2-Gy 剂量,23.3 对 34.5Gy;P=0.002)。在确定的 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%)发生了局部复发,这分别转化为 1 年局部控制率(LC)为 84%和 62%(P=0.009)。接受局限性(n=37)CART 后接受全面性 SRT(n=26)的患者总生存(51%对 12%;P=0.028)、无后续进展(31%对 0%;P<0.001)和无后续事件(19%对 0%;P=0.011)均优于接受局限性 SRT(n=11)的患者。
结论
与 r/r bNHL 患者中的 SRT 相比,BRT 后再接受 CART 似乎与更好的 LC 相关。尽管如此,如果给予全面性治疗,SRT 为 CART 后局限性(<5 个部位)复发提供了一种有前途的挽救性干预措施。