Kharfan-Dabaja Mohamed A, Kumar Ambuj, Pinilla-Ibarz Javier, Brown Jennifer R, Shadman Mazyar, Awan Farrukh T, Kenderian Saad S, Siddiqi Tanya, Abramson Jeremy S, Al-Juhaishi Taha, Brander Danielle M, Coombs Catherine C, Furman Richard R, Jain Nitin, Khan Nadia, Saba Nakhle S, Collins Jennifer M, Beitinjaneh Amer, Stephens Deborah M, Woyach Jennifer, Hamadani Mehdi
Division of Hematology-Oncology and Blood and Marrow Transplantation and Cellular Therapy Program, Mayo Clinic Comprehensive Cancer Center, Mayo Clinic, Jacksonville, Florida.
Research Methodology and Biostatistics Core, Office of Research Morsani College of Medicine, University of South Florida, Tampa, Florida.
Transplant Cell Ther. 2025 Jun 11. doi: 10.1016/j.jtct.2025.06.002.
Chimeric antigen receptor T-cell therapy (CAR T-cell) is a new treatment option for relapsed and/or refractory (R/R) chronic lymphocytic leukemia (CLL). Novel therapies including Bruton's tyrosine kinase inhibitors (BTK), covalent or noncovalent, and an inhibitor of the B-cell leukemia/lymphoma 2 protein (BCL-2), venetoclax, have replaced chemoimmunotherapy (CIT) regimens in the front-line and the R/R setting, and have relegated allogeneic hematopoietic cell transplantation (allo-HCT) to later treatment stages. Updating the 2016 clinical practice recommendations on allo-HCT in CLL is necessary to help guide contemporary clinical practice. A panel of 18 physicians with diverse expertise across different CLL treatment modalities and one methodologist participated in this effort. Any recommendation receiving ≥ 70% votes was considered a consensus. CAR T-cell therapy is recommended for patients not responding or relapsing after at least 2 lines of therapy consisting of a covalent BTK inhibitor and a BCL-2 inhibitor. In addition, CAR T-cell therapy is recommended for patients who subsequently received a noncovalent BTK inhibitor in the third-line or later setting, regardless of response. CAR T-cell therapy is also recommended in CLL relapsing after an allo-HCT, assuming that patients are fit for the procedure. In those CLL patients who are candidates, allo-HCT is recommended if disease is R/R to CAR T-cell therapy provided that an objective response is demonstrated prior to the allograft. Allo-HCT is also recommended in patients with clonally-related Richter transformation (RT) after demonstrating an objective response to front-line CIT or other treatments. CAR T-cell therapy is recommended in R/R RT. We emphasize the importance of enrolling patients in clinical trials whenever available to continue to advance the field and improve prognosis of R/R CLL. We acknowledge that there are unique clinical scenarios not covered herein which may require a case-by-case approach.
嵌合抗原受体T细胞疗法（CAR-T细胞疗法）是复发和/或难治性（R/R）慢性淋巴细胞白血病（CLL）的一种新的治疗选择。包括共价或非共价布鲁顿酪氨酸激酶抑制剂（BTK）以及B细胞淋巴瘤2蛋白（BCL-2）抑制剂维奈克拉在内的新型疗法，已在一线治疗和R/R治疗中取代了化学免疫疗法（CIT）方案，并将异基因造血细胞移植（allo-HCT）推迟到了后续治疗阶段。更新2016年关于CLL患者allo-HCT的临床实践建议，对于指导当代临床实践很有必要。一个由18名在不同CLL治疗模式方面具有不同专业知识的医生和一名方法学家组成的小组参与了这项工作。任何获得≥70%选票的建议都被视为达成共识。对于在接受至少2线由共价BTK抑制剂和BCL-2抑制剂组成的治疗后无反应或复发的患者，推荐使用CAR-T细胞疗法。此外，对于在三线或更晚治疗阶段随后接受了非共价BTK抑制剂治疗的患者，无论反应如何，均推荐使用CAR-T细胞疗法。对于allo-HCT后复发的CLL患者，假设患者适合该程序，也推荐使用CAR-T细胞疗法。在那些符合条件的CLL患者中，如果疾病对CAR-T细胞疗法R/R，但在同种异体移植前证明有客观反应，则推荐进行allo-HCT。在对一线CIT或其他治疗有客观反应后，对于患有克隆相关里氏转化（RT）的患者，也推荐进行allo-HCT。对于R/R RT患者，推荐使用CAR-T细胞疗法。我们强调，只要有可能，就应让患者参加临床试验，以继续推动该领域的发展并改善R/R CLL患者的预后。我们承认，本文未涵盖一些独特的临床情况，可能需要逐案处理。
