Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Department of Hematology, Cancer Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
Cancer Immunol Immunother. 2023 Jul;72(7):2245-2256. doi: 10.1007/s00262-023-03418-2. Epub 2023 Mar 4.
Identifying the temporal pattern of recurrence and prognostic biomarkers would further help improve the efficacy of chimeric antigen receptor (CAR) -T therapy.
We examined the prognoses of 119 patients after sequential infusion of anti-CD19 and anti-CD22, a cocktail of 2 single-target CAR (CAR19/22) T cells in an open-label, single-center clinical trial (ChiCTR-OPN-16008526). And we, from a 70-biomarker panel, identified candidate cytokines that might predict the treatment failure, including primary non-response (NR) and early relapse (ER).
In our study, 3 (11.5%) patients with B-cell acute lymphoblastic leukemia (B-ALL) and 9 (12.2%) cases of B-cell non-Hodgkin lymphoma (NHL) failed to respond to sequential CAR19/22 T-cell infusion (NR). A total of 11 (42.3%) B-ALL patients and 30 (52.7%) B-NHL patients had relapses during follow-up. Most recurrence events (67.5%) occurred within six months of sequential CAR T-cell infusion (ER). We found that macrophage inflammatory protein (MIP)-3α was a highly sensitive and specific prognostic predictor for patients with NR/ER and those attaining over-6-month remission. Patients who had higher MIP3α levels after sequential CAR19/22 T-cell infusion had significantly favorable progression-free survival (PFS) than their counterparts with relatively lower MIP3α expression. Our experiments demonstrated that MIP3α could enhance the therapeutic effect of CAR-T cells by promoting T-cell infiltration into and enriching memory-phenotype T cells in the tumor environment.
This study showed that relapse occurred mainly within six months after sequential CAR19/22 T-cell infusion. Moreover, MIP3α could act as a valuable post-infusion biomarker for identifying patients with NR/ER.
识别复发的时间模式和预后生物标志物将有助于进一步提高嵌合抗原受体 (CAR) -T 疗法的疗效。
我们在一项开放标签、单中心临床试验（ChiCTR-OPN-16008526）中检查了 119 例连续输注抗 CD19 和抗 CD22 （抗 CD19/22 的鸡尾酒疗法）后患者的预后。我们从 70 个生物标志物面板中确定了可能预测治疗失败的候选细胞因子，包括原发性无反应 (NR) 和早期复发 (ER)。
在我们的研究中，3 例急性 B 淋巴细胞白血病 (B-ALL) 和 9 例 B 细胞非霍奇金淋巴瘤 (B-NHL) 患者对序贯 CAR19/22 T 细胞输注无反应 (NR)。在随访期间，共有 11 例 B-ALL 患者 (42.3%) 和 30 例 B-NHL 患者 (52.7%) 复发。大多数复发事件（67.5%）发生在序贯 CAR T 细胞输注后 6 个月内（ER）。我们发现巨噬细胞炎症蛋白 (MIP)-3α 是 NR/ER 患者和获得超过 6 个月缓解患者的高度敏感和特异性预后预测因子。在接受序贯 CAR19/22 T 细胞输注后 MIP3α 水平较高的患者，无进展生存期（PFS）显著优于 MIP3α 表达水平相对较低的患者。我们的实验表明，MIP3α 通过促进 T 细胞浸润和丰富肿瘤微环境中的记忆表型 T 细胞，增强了 CAR-T 细胞的治疗效果。
本研究表明，在序贯 CAR19/22 T 细胞输注后 6 个月内主要发生复发。此外，MIP3α 可以作为识别 NR/ER 患者的有价值的输注后生物标志物。
