Hao Yuan-Yuan, Chen Pan-Pan, Yuan Xiang-Gui, Zhao Ai-Qi, Liang Yun, Liu Hui, Qian Wen-Bin
Department of Hematology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang Province, China.
World J Clin Cases. 2022 Jul 6;10(19):6555-6562. doi: 10.12998/wjcc.v10.i19.6555.
Diffuse large B-cell lymphoma (DLBCL) is curable with first-line chemoimmunotherapy but patients with relapsed/refractory (R/R) DLBCL still face a poor prognosis. For patients with R/R DLBCL, the complete response rate to traditional next-line therapy is only 7% and the median overall survival is 6.3 mo. Recently, CD19-targeting chimeric antigen receptor T cells (CAR-T) have shown promise in clinical trials. However, approximately 50% of patients treated with CAR-T cells ultimately progress and few salvage therapies are effective.
Here, we report on 7 patients with R/R DLBCL whose disease progressed after CAR-T infusion. They received a PD-1 inhibitor (sintilimab) and a histone deacetylase inhibitor (chidamide). Five of the 7 patients tolerated the treatment without any serious adverse events. Two patients discontinued the treatment due to lung infection and rash. At the 20-mo follow-up, the median overall survival of these 7 patients was 6 mo. Of note, there were 2 complete response rates (CRs) and 2 partial response rates (PRs) during this novel therapy, with an overall response rate (ORR) of 57.1%, and one patient had a durable CR that lasted at least 20 mo.
In conclusion, chidamide combined with sintilimab may be a choice for DLBCL patients progressing after CD19-targeting CAR-T therapy.
弥漫性大B细胞淋巴瘤(DLBCL)通过一线化疗免疫疗法可治愈,但复发/难治性(R/R)DLBCL患者的预后仍然较差。对于R/R DLBCL患者,传统二线治疗的完全缓解率仅为7%,中位总生存期为6.3个月。最近,靶向CD19的嵌合抗原受体T细胞(CAR-T)在临床试验中显示出前景。然而,接受CAR-T细胞治疗的患者中约有50%最终病情进展,且几乎没有有效的挽救疗法。
在此,我们报告7例R/R DLBCL患者,他们在接受CAR-T输注后病情进展。他们接受了一种PD-1抑制剂(信迪利单抗)和一种组蛋白去乙酰化酶抑制剂(西达本胺)。7例患者中有5例耐受治疗,未出现任何严重不良事件。2例患者因肺部感染和皮疹而停止治疗。在20个月的随访中,这7例患者的中位总生存期为6个月。值得注意的是,在这种新疗法期间有2例完全缓解(CR)和2例部分缓解(PR),总缓解率(ORR)为57.1%,1例患者有持续至少20个月的持久CR。
总之,西达本胺联合信迪利单抗可能是接受靶向CD19的CAR-T治疗后病情进展的DLBCL患者的一种选择。