As of 2026, the increasing evidence of the efficacy of CAR-T cell therapy is prompting comparisons with traditional stem cell transplantation methods. These therapies play distinct roles depending on the type of blood cancer and clinical context.
In large B-cell lymphoma (LBCL), CAR-T therapy has increasingly taken precedence over traditional salvage chemotherapy and autologous hemopoietic cell transplantation (auto-HCT) for patients with primary refractory or early-relapsed disease. For B-cell acute lymphoblastic leukemia (B-ALL), CAR-T provides durable control and can serve as a bridge to allogeneic HCT (allo-HCT). Meanwhile, in multiple myeloma, CAR-T therapy has expanded to first relapse and is currently being evaluated against frontline auto-HCT. In contrast, CAR-T remains investigational for acute myeloid leukemia (AML), where allo-HCT is still considered a primary treatment.
According to the latest activity survey by the European Society for Blood and Marrow Transplantation (EBMT) for the year 2024, a total of 47,204 hematopoietic cell transplantation procedures were recorded, with allo-HCT showing a 2.6% increase from the previous year. The usage of CAR-T therapy rose significantly by 24.5%, treating 6,082 patients, predominantly focusing on B-cell malignancies and myeloma.
Therapeutic Approaches
Different therapies contribute uniquely to antitumor effects. Auto-HCT allows high-dose therapy without leading to prolonged marrow failure, as the patient’s own stem cells are reinfused after the treatment. Conversely, allo-HCT benefits from donor-derived immune activity that targets malignant cells based on multiple antigenic signals, while also carrying risks such as graft-versus-host disease (GVHD) and infections.
CAR-T cells are specifically engineered to target surface antigens, with CD19 and B-cell maturation antigen (BCMA) being notable examples. However, the long-term effectiveness of CAR-T can be hindered by factors like antigen loss, T-cell exhaustion, and a suppressive microenvironment. Acute and chronic toxicities are also associated with this type of therapy.
The landscape of treatment for LBCL has shifted significantly due to CAR-T therapy’s efficacy. Traditional treatment involved salvage chemoimmunotherapy followed by auto-HCT, but this strategy has proven less effective in cases of primary refractory and early-relapsed lymphoma. The ZUMA-7 trial compared axicabtagene ciloleucel (axi-cel) to standard salvage therapy, revealing a 54.6% estimated four-year overall survival rate with CAR-T compared to 46% with standard treatment.
In B-ALL, the relation to allo-HCT remains intricate, as both CAR-T and allo-HCT can induce profound remissions. The ZUMA-3 trial demonstrated that brexucabtagene autoleucel resulted in high remission rates in adults with the disease, albeit findings were exploratory and non-randomized.
Despite CAR-T’s successes, challenges remain, particularly in AML and T-ALL, due to overlapping antigens found on both cancerous and normal cells. Gene editing approaches are under investigation to address these challenges and improve CAR-T efficacy.
As advancements in CAR-T technology continue, the medical community is watching closely to see how these innovative treatments will reshape the boundaries of existing protocols and improve patient outcomes in hematologic malignancies.
