Negishi Shuto, Girsch James H, Siegler Elizabeth L, Bezerra Evandro D, Miyao Kotaro, Sakemura R Leo
Department of Hematology and Oncology, Konan Kosei Hospital, Konan, Japan.
T Cell Engineering, Mayo Clinic, Rochester, MN, United States.
Front Pediatr. 2024 Jan 12;11:1305657. doi: 10.3389/fped.2023.1305657. eCollection 2023.
Clinical trials of anti-CD19 chimeric antigen receptor T (CART19) cell therapy have shown high overall response rates in patients with relapsed/refractory B-cell malignancies. CART19 cell therapy has been approved by the US Food and Drug Administration for patients who relapsed less than 12 months after initial therapy or who are refractory to first-line therapy. However, durable remission of CART19 cell therapy is still lacking, and 30%-60% of patients will eventually relapse after CART19 infusion. In general, the prognosis of patients who relapse after CART19 cell therapy is poor, and various strategies to treat this patient population have been investigated extensively. CART19 failures can be broadly categorized by the emergence of either CD19-positive or CD19-negative lymphoma cells. If CD19 expression is preserved on the lymphoma cells, a second infusion of CART19 cells or reactivation of previously infused CART19 cells with immune checkpoint inhibitors can be considered. When patients develop CD19-negative relapse, targeting different antigens (e.g., CD20 or CD22) with CAR T cells, investigational chemotherapies, or hematopoietic stem cell transplantation are potential treatment options. However, salvage therapies for relapsed large B-cell lymphoma after CART19 cell therapy have not been fully explored and are conducted based on clinicians' case-by-case decisions. In this review, we will focus on salvage therapies reported to date and discuss the management of relapsed/refractory large B-cell lymphomas after CART19 cell therapy.
抗CD19嵌合抗原受体T(CART19)细胞疗法的临床试验表明,复发/难治性B细胞恶性肿瘤患者的总体缓解率较高。CART19细胞疗法已获美国食品药品监督管理局批准,用于初始治疗后复发少于12个月或一线治疗难治的患者。然而,CART19细胞疗法仍缺乏持久缓解,30%-60%的患者在输注CART19后最终会复发。一般来说,CART19细胞疗法后复发患者的预后较差,针对这一患者群体的各种治疗策略已得到广泛研究。CART19治疗失败可大致分为CD19阳性或CD19阴性淋巴瘤细胞的出现。如果淋巴瘤细胞上保留CD19表达,可以考虑再次输注CART19细胞或用免疫检查点抑制剂重新激活先前输注的CART19细胞。当患者出现CD19阴性复发时,用CAR T细胞靶向不同抗原(如CD20或CD22)、试验性化疗或造血干细胞移植是潜在的治疗选择。然而,CART19细胞疗法后复发的大B细胞淋巴瘤的挽救治疗尚未得到充分探索,且是根据临床医生的逐案决定进行的。在本综述中,我们将重点关注迄今为止报道的挽救治疗,并讨论CART19细胞疗法后复发/难治性大B细胞淋巴瘤的管理。
Front Pediatr. 2024-1-12
Mol Ther Methods Clin Dev. 2024-12-5