Department of Medical Oncology, Inselspital, Bern University Hospital, 3010 Bern, Switzerland.
Department of Hematology and Central Hematology Laboratory, Inselspital, Bern University Hospital, 3010 Bern, Switzerland.
Cells. 2022 Sep 2;11(17):2747. doi: 10.3390/cells11172747.
Mantle cell lymphoma (MCL) is a rare type of B-cell Non-Hodgkin lymphoma (NHL) affecting predominantly male patients. While complete remissions following first-line treatment are frequent, most patients ultimately relapse, with a usually aggressive further disease course. The use of cytarabine-comprising induction chemotherapy and autologous stem cell transplantation, Rituximab maintenance, Bruton's tyrosine kinase (BTK) inhibitors and CAR T therapy has substantially improved survival. Still, options for patients relapsing after CAR T therapy are limited and recommendations for the treatment of these patients are lacking. We report two cases of patients with mantle cell lymphoma who relapsed after CAR T therapy and were treated with the bispecific CD20/CD3 T cell engaging antibody glofitamab. Both patients showed marked increases of circulating CAR T cells and objective responses after glofitamab administration. Therapy was tolerated without relevant side effects in both patients. One patient completed all 12 planned cycles of glofitamab therapy and was alive and without clinical progression at the last follow-up. The second patient declined further treatment after the first cycle and succumbed to disease progression. We review the literature and investigate possible mechanisms involved in the observed responses after administration of glofitamab, such as proliferation of CAR T cells, anti-tumor effects of the bispecific antibody and the role of other possibly contributing factors. Therapy with bispecific antibodies might offer an effective and well-tolerated option for patients with mantle cell lymphoma relapsing after CAR T therapy.
套细胞淋巴瘤（MCL）是一种罕见的 B 细胞非霍奇金淋巴瘤（NHL），主要影响男性患者。虽然一线治疗后常可达到完全缓解，但大多数患者最终会复发，疾病进展通常具有侵袭性。阿糖胞苷为基础的诱导化疗和自体干细胞移植、利妥昔单抗维持、布鲁顿酪氨酸激酶（BTK）抑制剂和嵌合抗原受体 T 细胞（CAR T）治疗的应用显著改善了患者的生存。然而，CAR T 治疗后复发患者的选择有限，且缺乏这些患者的治疗建议。我们报告了两例接受 CAR T 治疗后复发的套细胞淋巴瘤患者，他们接受了双特异性 CD20/CD3 T 细胞结合抗体 glofitamab 的治疗。两名患者在接受 glofitamab 治疗后均表现出循环 CAR T 细胞显著增加和客观缓解。两名患者均耐受了治疗，无相关副作用。一名患者完成了 glofitamab 治疗的所有 12 个周期，在最后一次随访时仍存活且无临床进展。第二名患者在接受第一个周期治疗后拒绝进一步治疗，死于疾病进展。我们回顾了文献，并探讨了 glofitamab 给药后观察到的反应可能涉及的机制，如 CAR T 细胞的增殖、双特异性抗体的抗肿瘤作用以及其他可能起作用的因素的作用。双特异性抗体治疗可能为 CAR T 治疗后复发的套细胞淋巴瘤患者提供一种有效且耐受良好的选择。
