CAR-T治疗复发 难治性大B细胞淋巴瘤失败后的临床分析

Clinical analysis of CD19 chimeric antigen receptor-T cell treatment failure in relapsed or refractory large B-cell lymphoma

  • 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。

     

    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.

     

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