Shumilov Evgenii, Scholz Julia Katharina, Seib Maximilian, Mazzeo Paolo, Wurm-Kuczera Rebecca, Vucinic Vladan, Holtick Udo, Boyadzhiev Hristo, Melchardt Thomas, Hölscher Alexander, Schultze-Florey Christian, Abdelhafez Atef, Velazquez Giuliano Filippini, Ossami Saidy Anna, Lesan Vadim, Schnetzke Ulf, Kerkhoff Andrea, Bacher Ulrike, Ghandili Susanne, Aydilek Enver, Gebauer Niklas, Weber Thomas, Wulf Gerald, Glass Bertram, Thurner Lorenz, Heidel Florian H, Schmid Christoph, Viardot Andreas, Hänel Mathias, Dietrich Sascha, Pabst Thomas, Ayuk Francis, von Tresckow Bastian, Chapuy Björn, Pott Christiane, Müller Fabian, Lenz Georg
Department of Medicine A, Hematology, Oncology and Pneumology, University Hospital Muenster, Muenster, Germany.
Department of Internal Medicine 5, Hematology and Oncology, University Hospital of Erlangen, Erlangen, Germany.
Blood Adv. 2025 Aug 12;9(15):3955-3966. doi: 10.1182/bloodadvances.2024015719.
Patients with large B-cell lymphoma (LBCL) who experience relapsed disease after CD19-directed chimeric antigen receptor (CAR) T-cell (CAR-T) therapy have a poor prognosis. Bispecific antibodies (BsAbs) induce complete remissions in ∼35% of these cases. Hypothesizing overlapping LBCL-intrinsic resistance mechanisms as well as common poor prognosis predictors to CAR-T and BsAb therapy, we conducted a multicenter retrospective analysis including 92 patients with relapsed/refractory (R/R) LBCL treated with BsAbs after CAR-T failure. Overall response rate (ORR) was 43%, with a progression-free survival (PFS) of 2.8 months. Patients receiving BsAbs during early relapse (≤3 months) achieved a significantly worse outcome (ORR, 29%; PFS, 2.2 months) compared with patients with an intermediate (4-6 months; ORR, 54%; PFS, 3.7 months) or a late relapse (>6 months; ORR, 60%; PFS, 10.5 months). The benefit of later relapse was particularly notable in patients receiving BsAbs as first salvage therapy compared with those receiving a BsAb in subsequent lines (PFS not reached vs 2.7 months; overall survival not reached vs 9.1 months, respectively). In addition to early R/R state before BsAbs, elevated lactate dehydrogenase and higher International Prognostic Index score were significant predictors of poor outcomes to BsAb in multivariate Cox regression analyses. The finding that patients with early relapse after CAR-T respond particularly poorly to BsAb highlights the necessity for alternative treatment options in this high-risk patient cohort.
在接受靶向CD19的嵌合抗原受体（CAR）T细胞（CAR-T）治疗后出现疾病复发的大B细胞淋巴瘤（LBCL）患者预后较差。双特异性抗体（BsAbs）在约35%的此类病例中可诱导完全缓解。鉴于推测LBCL存在重叠的内在耐药机制以及CAR-T和BsAb治疗共同的不良预后预测因素，我们进行了一项多中心回顾性分析，纳入了92例在CAR-T治疗失败后接受BsAbs治疗的复发/难治性（R/R）LBCL患者。总缓解率（ORR）为43%，无进展生存期（PFS）为2.8个月。与复发时间为中期（4 - 6个月；ORR，54%；PFS，3.7个月）或晚期（>6个月；ORR，60%；PFS，10.5个月）的患者相比，在早期复发（≤3个月）时接受BsAbs治疗的患者预后明显更差（ORR，29%；PFS，2.2个月）。与在后续治疗线中接受BsAbs治疗的患者相比，作为首次挽救治疗接受BsAbs治疗的患者，晚期复发的获益尤为显著（PFS未达到 vs 2.7个月；总生存期未达到 vs 9.1个月）。在多变量Cox回归分析中，除了在使用BsAbs之前处于早期R/R状态外，乳酸脱氢酶升高和国际预后指数评分较高是BsAb治疗预后不良的显著预测因素。CAR-T治疗后早期复发的患者对BsAb反应特别差这一发现凸显了在这一高风险患者队列中采用替代治疗方案的必要性。
