肿瘤细胞治疗研究
英文原题：Long-Term Outcomes of Second Allogeneic Transplantation Following CD7 CAR-T in Remission for T-Cell Acute Lymphoblastic Leukemia or Lymphoma.
本研究纳入 24 例（21 例 T-ALL，3 例 T-LBL）在首次 allo-HSCT 后复发且在本中心接受自然选择 CD7 CAR-T（NS7CAR-T）治疗的患者，细胞来源为患者来源（n = 18）或既往移植供者来源（n = 6）。
异基因造血干细胞移植（allo-HSCT）后复发的T细胞急性淋巴细胞白血病/淋巴瘤（T-ALL/LBL）患者治疗选择有限且预后不良。靶向CD7的CAR-T 细胞疗法已在T-ALL/LBL中显示较高缓解率，但对于移植后复发且接受CAR-T治疗后再进行第二次移植的患者，其安全性和疗效仍研究不足。本文报告来自I/II期临床试验（NCT04572308和NCT04916860）的移植后复发T-ALL/LBL患者接受CD7 CAR-T治疗的疗效和安全性，并首次全面分析CD7 CAR-T治疗后第二次allo-HSCT的长期结局。本研究旨在分析CD7 CAR-T后第二次移植的预后，以及CD7 CAR-T用于移植后复发患者的安全性。研究纳入24例首次allo-HSCT后复发并在本中心接受天然筛选CD7 CAR-T（NS7CAR-T）治疗的患者（T-ALL 21例，T-LBL 3例）；细胞来源于患者自身（n=18）或既往移植供者（n=6）。患者随后接受或未接受第二次allo-HSCT。我们分析NS7CAR-T疗效和安全性，以及第二次移植后的生存、复发和移植相关并发症。NS7CAR-T治疗后，23例中21例（91.3%）在骨髓中达到微小残留病（MRD）阴性完全缓解（CR）。13例伴髓外病变（EMD）患者中，8例（61.5%）达到CR。NS7CAR-T治疗后，18例接受第二次allo-HSCT，其余6例未移植。第二次移植前，所有患者骨髓均为MRD阴性，但1例仍有EMD。第二次移植后中位随访510天（范围32–1,352天）。18例患者的3年总生存率（OS）为46.4%，3年无白血病生存率（LFS）为44.4%。3年复发累积发生率为16.7%，3年非复发死亡率（NRM）为48.0%。相较之下，未接受第二次移植的6例患者均死亡，CAR-T输注后的中位生存期为102天。NS7CAR-T治疗在移植后复发T-ALL/LBL患者中显示出较高CR率。第二次移植巩固治疗似乎可行，可能为这些经多线治疗的患者提供有前景的治疗策略。但较高NRM提示仍需进一步努力降低这一风险。未接受巩固移植患者的结局均较差。
Patients with T-cell acute lymphoblastic leukemia or lymphoma (T-ALL/LBL) who relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) face limited treatment options and a poor prognosis. While CD7-targeted chimeric antigen receptor T-cell (CAR-T) therapy has demonstrated high remission rates in T-ALL/LBL, its safety and efficacy in post-transplant relapse remain underexplored in patients who experience post-transplant relapse and subsequently undergo a second transplant after CAR-T treatment. Here, we report the efficacy and safety of CD7 CAR-T in T-ALL/LBL patients who relapsed post-transplant from the phase I/II clinical trials (https://clinicaltrials.gov/ NCT04572308 and NCT04916860), and provide the first comprehensive analysis of long-term outcomes following a second allo-HSCT after CD7 CAR-T treatment. To analyze the prognosis of second transplant post-CD7 CAR-T and safety of CD7 CAR-T in T-ALL/LBL patients who relapsed post-transplant. This study included 24 patients (21 T-ALL, 3 T-LBL) who relapsed after first allo-HSCT and received naturally selected CD7 CAR-T (NS7CAR-T) therapy from patient-derived (n = 18) or prior transplant donor-derived (n = 6) at our center. Patients either proceeded to a second allo-HSCT or not. We analyzed NS7CAR-T efficacy and safety, survival, relapse, and transplant-related complications following second transplant. After NS7CAR-T, 21/23 (91.3%) achieved minimal residual disease (MRD)-negative CR in bone marrow (BM). For the 13 patients with extramedullary disease (EMD), 8 (61.5%) achieved CR. Following NS7CAR-T, 18 patients proceeded to a second allo-HSCT, while the remaining 6 did not. Prior to second transplant, all patients were MRD-negative in BM but one had persistent EMD. The median follow-up after second transplant was 510 days (range: 32 to 1352). For the 18 patients, the 3-year overall survival (OS) was 46.4%, and the 3-year leukemia-free survival (LFS) was 44.4%. The 3-year cumulative incidence of relapse was 16.7%, and the 3-year nonrelapse mortality (NRM) was 48.0%. In contrast, all 6 patients who did not undergo a second transplant died, with a median survival of 102 days post-CAR-T infusion. NS7CAR-T therapy showed a high CR rate for T-ALL/LBL patients who relapsed post-transplant. Consolidation with a second transplant appears feasible and may offer a promising therapeutic strategy for these heavily pretreated patients. However, the high NRM demonstrated the need for further efforts to mitigate this risk. Patients who did not receive consolidative transplantation experienced uniformly poor outcomes.
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