Clinical analysis of CD19 chimeric antigen receptor-T cell treatment failure in relapsed or refractory large B-cell lymphoma
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摘要:
目的 探讨真实世界大B细胞淋巴瘤（large B-cell lymphoma，LBCL）嵌合抗原受体-T（chimeric antigen receptor-T，CAR-T）细胞治疗失败后的结局。 方法 回顾性分析2018年7月至2022年12月于南昌大学第一附属医院接受CD19 CAR-T细胞治疗后出现疾病复发/难治性16例LBCL患者的临床资料，分析其后续治疗和预后。 结果 16例患者中男性10例、女性6例，中位年龄53.5（16～72）岁，其预后极差，中位总生存期（median overall survival，mOS）仅为5.7个月（95%CI：5.1～6.3）。积极后续抗肿瘤治疗患者12例（75%），mOS为9.8个月（95%CI：3.3～16.3）；姑息治疗4例（25%），mOS仅为2.1个月（95%CI：0～4.8），差异具有统计学意义（P<0.05）。后续抗肿瘤方案包括Pola-BR为4例（33.3%）、BTK抑制剂4例（33.3%）、抗PD-1抗体2例（16.7%）和免疫化疗2例（16.7%），最佳疗效为部分缓解4例（33.3%）。BTK抑制剂组2例（50%）为部分缓解，mOS为10.8个月（95%CI：3.4～18.1），较其他方案似有获益趋势，但差异无统计学意义（P>0.05）。 结论 CAR-T治疗后复发或进展的LBCL患者预后差，治疗手段局限，如何合理化分层使用后线治疗策略未来值得探索。 -
关键词:
- 嵌合抗原受体修饰T细胞 /
- 复发/难治性大B细胞淋巴瘤 /
- 挽救性治疗
Abstract:Objective To analyze real-word experience of patients with relapsed/refractory large B-cell lymphoma (LBCL) after failure of chimeric antigen receptor-T (CAR-T) cell therapy. Methods We retrospectively evaluated clinical outcomes and salvage therapies from 16 patients who relapsed or progressed following CD19 CAR-T cell therapy at The First Affiliated Hospital of Nanchang University between July 2018 and December 2022. Results The cohort had 10 males and 6 females, with a median age of 53.5 years (range, 16-72).The prognosis of these patients was extremely poor, with a median overall survival (mOS) of only 5.7 months (95% confidence interval [CI]: 5.1-6.3). Compared with supportive or palliative care exhibiting a mOS of 2.1 months (n=4, 95%CI: 0–4.8), subsequent antitumor therapies (n=12) were associated with a statistically significant survival benefit, with a mOS of 9.8 months (95%CI: 3.3–16.3, P<0.05). Next-line antitumor regimens included Pola-BR (n=4, 33.3%), BTK inhibitor (n=4, 33.3%), anti-PD-1 antibody (n=2, 16.7%), and conventional immune-chemotherapy (n=2, 16.7%), witha partial response observed in four patients (33.3%). For the BTK inhibitor- based treatment, two cases (50%) exhibited a partial response, and the mOS was 10.8 months (95% CI: 3.4-18.1), which showed a trend of superiority compared with the other regimens (P>0.05). Conclusions CAR-T cell therapy failure demonstrated a very poor prognosis and the treatment options were very limited for patients with LBCL. Further research is needed to determine the optimal salvage regimen following failure of CAR-T cell therapy. -
表 1 16例CAR-T细胞治疗后出现疾病复发或进展的复发/难治性LBCL患者临床特征及后续治疗
患者
编号年龄（岁） 性别 疾病
分期（期）IP评分（分） 大包块 既往化疗
线数 （线 ）原发
难治诊断到
接受CAR-T
治疗时间（月）CAR-T
最佳疗效CAR-T失败到
后续治疗
时间（月）后续
治疗方案后续治疗
最佳疗效CAR-T治疗
失败后OS（月）生存
状态P1 66 男 Ⅳ 3 否 2 是 18 SD 4.2 BTK抑制剂 PR 16.8 死亡 P2 64 女 Ⅲ 3 否 2 否 24 PR 6.3 Pola-BR PD 4.1 死亡 P3 62 男 未知 未知 否 3 否 21 PR 5.2 Pola-BR SD 10.9 死亡 P4 55 男 Ⅲ 3 是 2 是 12 SD 3.9 免疫化疗 PR 11.2 死亡 P5 55 女 Ⅲ 3 否 2 否 6 PD 1.2 抗PD-1抗体 PD 2.4 死亡 P6 54 女 Ⅳ 4 否 2 否 15 SD 3.2 BTK抑制剂 SD 10.8 死亡 P7 53 女 Ⅲ 5 是 2 否 13 PR 5.7 BTK抑制剂 PD 5.9 死亡 P8 52 女 Ⅱ 2 是 3 否 36 PD 1.5 免疫化疗 PD 5.6 死亡 P9 50 女 Ⅳ 3 是 2 否 15 CR 6.0 BTK抑制剂 PR 10.4 存活 P10 45 男 Ⅳ 3 否 3 否 32 PD 3.2 抗PD-1抗体 PD 9.8 死亡 P11 21 男 未知 未知 是 2 是 10 PD 2.2 Pola-BR PD 3.8 死亡 P12 50 男 Ⅲ 3 是 3 是 14 CR 15.0 Pola-BR PR 6.1 存活 P13 70 男 Ⅳ 4 是 2 是 10 SD 不适用 不适用 不适用 1.5 死亡 P14 16 男 未知 未知 是 5 是 8 SD 不适用 不适用 不适用 2.1 死亡 P15 72 男 Ⅳ 3 是 2 是 4 PD 不适用 不适用 不适用 4.3 死亡 P16 45 男 Ⅱ 2 否 4 否 30 PD 不适用 不适用 不适用 5.7 死亡 
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表 2 CAR-T治疗失败后后续治疗的缓解情况
评效 Pola-BR（n=4） BTK抑制剂（n=4） 抗PD-1抗体（n=2） 免疫化疗（n=2） ORR（%） 25 50 0 50 CR（%） 0 0 0 0 DCR（%） 50 75 0 50
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