Editor’s Note: Cellular therapy has emerged as a breakthrough treatment modality, showing remarkable efficacy across various hematologic malignancies. However, its application in chronic lymphocytic leukemia (CLL) continues to face notable challenges.
At the 2025 China Research Hospital Association Conference on Cellular Therapy and Biomedical Frontiers, held in Xiong’an from October 31 to November 1, 2025, Professor Micha Srour from Lille University Hospital (France) delivered a keynote lecture titled “Advances in Cellular Therapy for CLL.” In his talk, Professor Srour comprehensively reviewed the latest scientific and clinical progress in CLL-focused cell therapy research.
Following his presentation, Oncology Frontier – Hematology Frontier conducted an exclusive interview with Professor Srour, discussing in depth the current status, major challenges, and future prospects of CAR-T cell therapy in CLL.
Prof. Micha SROUR: As of now, the latest data from the TRANSCEND 0004 study have been released. These results led to FDA approval of the autologous CD19-directed chimeric antigen receptor (CAR) T-cell therapy lisocabtagene maraleucel (liso-cel) for the treatment of patients with chronic lymphocytic leukemia (CLL). However, it has not yet been approved in Europe or other regions.
For CLL patients who relapse after treatment with B-cell lymphoma-2 (BCL-2) inhibitors and Bruton tyrosine kinase (BTK) inhibitors, therapeutic options remain extremely limited. To address this unmet clinical need, researchers continue to explore novel strategies, with CAR-T cell therapy holding considerable promise.
Nevertheless, the application of CAR-T therapy in CLL faces significant challenges. Unlike in other B-cell malignancies, insufficient CAR-T cell expansion in CLL patients is a key factor limiting efficacy. To tackle this issue, the team led by Jordan Gauthier at the Hutchinson Cancer Research Center in France conducted in-depth research, attempting to enhance CAR-T cell expansion by combining ibrutinib administration before apheresis and after CAR-T cell infusion. The results demonstrated that this approach significantly improved CAR-T cell expansion levels and rates, as well as overall response rates in patients. However, compared to the durable response “plateau” observed in diffuse large B-cell lymphoma (DLBCL), CLL patients have not yet achieved similar sustained responses, indicating that further optimization of CAR-T therapy efficacy in CLL is still required.
CLL is a highly refractory disease, particularly in patients harboring TP53 mutations or developing resistance to BTK or BCL-2 inhibitors, where clinical management is especially challenging. Encouragingly, the emergence of next-generation BTK inhibitors offers new solutions to this problem. Just as ponatinib successfully overcomes the T315I mutation in chronic myeloid leukemia (CML), innovative BTK inhibitors in the future are expected to play a critical role in addressing drug-resistant mutations in CLL.
Overall, CAR-T therapy has yet to demonstrate ideal efficacy in CLL treatment and is unlikely to gain approval in Europe in the near term. Meanwhile, novel immunotherapies such as bispecific antibodies are gradually entering the CLL treatment landscape, showing promising prospects. With the continuous emergence of various innovative therapies, it is anticipated that reliance on cellular therapies may be reduced in certain patient populations in the future.
Additionally, for select young patients in good physical condition with TP53 mutations or del(17p) abnormalities, allogeneic hematopoietic stem cell transplantation remains a viable treatment option, potentially offering longer-term survival benefits.
