决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:BCMA CAR-T induces complete and durable remission in refractory plasmablastic lymphoma.
浆母细胞淋巴瘤(PBL)是一种罕见的侵袭性大B细胞淋巴瘤亚型,尽管采用积极治疗,预后仍然很差。
浆母细胞淋巴瘤(PBL)是一种罕见的侵袭性大B细胞淋巴瘤亚型,尽管采用积极治疗,预后仍然很差。对于难治性疾病患者,需要新的治疗方法。PBL表达与多发性骨髓瘤(MM)相似的抗原,包括B细胞成熟抗原(BCMA)。在一项Ib/II期试验(A Study of JNJ-68284528, a CAR-T Directed Against BCMA in Participants With Relapsed or Refractory Multiple Myeloma (CARTITUDE-1), NCT03548207)中,针对BCMA的CAR-T 细胞疗法已显示出对经过大量预治疗的MM具有疗效,且3级和4级细胞因子释放综合征(CRS)和免疫效应细胞相关神经毒性综合征(ICANS)的发生率较低。然而,关于使用BCMA CAR-T治疗PBL的数据尚缺乏。我们报告了一例具有挑战性的多发性难治性PBL病例,该病例发生于一例青少年B细胞急性淋巴细胞白血病患者,且对异基因造血细胞移植无应答。尽管停用免疫抑制治疗并接受依托泊苷、依鲁替尼和达雷妥尤单抗治疗,患者仍出现疾病快速进展,促使考虑使用BCMA CAR-T(根据紧急研究性新药(eIND))。患者在接受BCMA CAR-T治疗后达到完全缓解(CR),未出现复发性急性移植物抗宿主病(GVHD)、CRS或ICANS。在体内检测到BCMA CAR-T扩增,于第15天达到峰值。患者在CAR-T治疗后保持CR超过一年,支持考虑将免疫治疗用于未来难治性PBL患者,这是一种治疗选择很少的疾病。
Plasmablastic lymphoma (PBL) is a rare subtype of aggressive large B-cell lymphoma, with a dismal prognosis despite aggressive therapies. New approaches are needed for those with refractory disease. PBL expresses antigens similar to multiple myeloma (MM), including B-cell maturation antigen (BCMA). Chimeric antigen receptor T-cell (CAR-T) therapy directed against BCMA has shown efficacy for the treatment of heavily pretreated MM with low rates of grades 3 and 4 cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) in a phase Ib/II trial (A Study of JNJ-68284528, a CAR-T Directed Against BCMA in Participants With Relapsed or Refractory Multiple Myeloma (CARTITUDE-1), NCT03548207). However, data for the use of BCMA CAR-T for treating PBL are lacking.We report a challenging case of multiple refractory PBL that emerged from B-cell acute lymphoblastic leukemia in an adolescent who failed to respond to an allogeneic hematopoietic cell transplant. The patient developed rapidly advancing disease despite withdrawal of immunosuppression, treatment with etoposide, ibrutinib, and daratumumab, prompting consideration of BCMA CAR-T (under emergency investigational new drug (eIND)). The patient achieved a complete remission (CR), without recurrent acute graft versus host disease (GVHD), CRS or ICANS after BCMA CAR-T therapy. BCMA CAR-T expansion was detected in vivo, peaking on day 15. The patient remains in CR for more than a year post CAR-T therapy, supporting consideration of immunotherapy for future patients with refractory PBL, a disease with few treatment options.
MEMBER ACCOUNT
登录成功会直接打开下一页。