Dr. Hu from GoBroad Healthcare Group- Beijing GoBroad Hospital provides a professional overview on the combined application of CAR-T cell therapy and transplantation.

CAR-T Combined With Transplantation: Achieving Deep Remission and Long-Term Survival in Hematologic Malignancies

Q: The emergence of CAR-T cell therapy has significantly changed the treatment landscape for B-cell lymphomas. Could you first introduce the current status of combined CAR-T therapy and transplantation?

Dr. Hu: Recent clinical practice has demonstrated that CAR-T cell therapy provides excellent efficacy for large B-cell lymphoma and other B-cell malignancies. However, a subset of patients still experiences disease progression after CAR-T infusion, primarily due to insufficient depth of remission.

To address this challenge, the strategy of “CAR-T cell therapy combined with hematopoietic stem cell transplantation” has emerged. Although not yet widely adopted, this combined approach can achieve deeper remission in selected populations—especially those who remain chemo-sensitive.

With increasing clinical experience, our management of CAR-T-related toxicities has become more refined, laying a solid foundation for the safe integration of these two therapies. Thus, this combined strategy holds great promise for helping patients achieve long-term survival and potentially a cure.

“Bridging” and “Consolidation”: Synergy and Balance Between Two Key Strategies

Q: “CAR-T as a bridge to transplantation” and “post-transplant CAR-T consolidation” are the two main strategies for combined therapy. How do they achieve the synergistic effect of “1+1>2”? What should be considered in balancing efficacy and toxicity when using post-transplant CAR-T consolidation? Any clinical insights?

Dr. Hu: Although both “CAR-T bridging to transplantation” and “post-transplant CAR-T consolidation” integrate CAR-T therapy with transplantation, the target populations of the two strategies differ.

“CAR-T bridging transplantation” is mainly intended for high-risk patients who are prone to relapse after CAR-T cell therapy, such as acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma. These patients may achieve a good response after CAR-T therapy, creating an opportunity for subsequent allogeneic transplantation. For patients stratified as high-risk for relapse, bridging to transplantation after CAR-T therapy helps achieve eventual cure.

“Post-transplant CAR-T consolidation” is mainly used for lymphoma or myeloma patients who undergo autologous hematopoietic stem cell transplantation. After high-dose chemotherapy and transplantation, highly sensitive testing may still detect minimal residual disease (MRD). These residual tumor cells are often resistant to chemotherapy. At this point, using CAR-T cell therapy as consolidation can eliminate MRD, achieve deeper remission, prolong survival, and even lead to cure.

Overall, both “CAR-T bridging transplantation” and “post-transplant CAR-T consolidation” target specific patient groups, with the shared goal of achieving deep remission and eventual cure. The reason these two strategies produce a “1 + 1 > 2” synergistic effect is twofold:

• CAR-T cell therapy offers complete remission opportunities for patients who are insensitive to chemotherapy;
• Pre-transplant high-dose chemotherapy clears the immunosuppressive microenvironment, supporting CAR-T cell expansion and persistence.

Meanwhile, for many patients, although hematopoietic stem cell transplantation does not achieve complete remission, it significantly reduces tumor burden, creating more favorable conditions for subsequent CAR-T therapy and enhancing its efficacy.

In terms of safety, the toxicity profiles of the two therapies differ: transplantation toxicity mainly arises from high-dose chemotherapy and graft-versus-host disease (GVHD) in allogeneic transplantation; CAR-T-related toxicities mainly include cytokine release syndrome (CRS) and immune-effector-cell–associated neurotoxicity syndrome (ICANS). In recent years, through prophylactic management, early intervention, and the application of new therapies, our ability to control these adverse events has greatly improved, and the safety of combined treatment continues to increase.

Future Pathway: Precise Patient Selection as the Key to Deep Integration

Q: Looking ahead, where do you see the major trends and breakthroughs in the deep integration of CAR-T therapy and transplantation?

Dr. Hu: From a technical standpoint, both CAR-T cell therapy and transplantation are already highly mature modalities. To further enhance the value of combined treatment in the future, the most critical breakthrough lies in precise patient selection. Our primary task is to accurately identify those high-risk patients who can truly benefit the most from such combined therapy, while avoiding unnecessary overtreatment.
Achieving this goal depends on advanced diagnostic technologies. In the future, we must make deeper use of genomics, molecular biology testing, and high-precision MRD monitoring to dynamically and accurately assess patients’ relapse risks before, during, and after treatment. Using these objective tools, together with patients' clinical characteristics, we can identify early those who “most need” combined therapy and tailor treatment strategies specifically for them.
In summary, the technology itself is not the bottleneck. The key lies in selecting the right patients and providing individualized treatment plans, thereby achieving deep integration of CAR-T and transplantation—and truly moving toward cure.