The 67th Annual Meeting of the American Society of Hematology (ASH) was held in Orlando, USA, showcasing the latest research and clinical advances in the field of hematology. At this year’s meeting, the team led by Professor Kai Hu from GoBroad Healthcare Group had seven studies accepted for presentation. These studies focused on CAR-T therapy in various types of relapsed/refractory lymphoma, including B-cell lymphoma, central nervous system lymphoma (CNSL), T-cell lymphoma, as well as combined strategies integrating CAR-T therapy with hematopoietic stem cell transplantation. Professor Hu provided a systematic interpretation of these research findings.

Q1. What were the main studies presented by your team at this year’s ASH meeting, and which “key clinical questions” did they aim to address?

All seven studies we presented this year revolve around a single core objective: to make CAR-T therapy more effective, more predictable, and more actionable in high-risk patient populations, with clear strategies for subsequent treatment steps.

Overall, these studies can be summarized into three main lines of investigation.

First, prospective studies targeting key refractory disease subtypes, resembling rigorously designed clinical trials. These include:

• A phase I study of CD19 CAR-T therapy in relapsed/refractory central nervous system lymphoma (CNSL)
• A phase I study of CD7 CAR-T therapy in T-cell acute lymphoblastic leukemia/lymphoblastic lymphoma (T-ALL/LBL), with long-term follow-up

Both disease entities have limited treatment options and are particularly difficult to manage after relapse, making prospective evidence essential to address fundamental questions such as feasibility, efficacy, and safety.

Second, what should be done after failure of CD19 CAR-T therapy?
CAR-T therapy is not effective for all patients. We explored salvage strategies using hematopoietic stem cell transplantation after CAR-T failure and compared outcomes between autologous and allogeneic transplantation cohorts, aiming to provide evidence-based guidance for post–CAR-T treatment decision-making.

Third, can treatment response be predicted earlier, and are there actionable biomarkers?
We investigated several potential biomarkers associated with treatment outcomes, including:

• The presence of TP53 mutations in tumor cells
• Dynamic changes in PD-1 expression on CAR-T cells and their in vivo exhaustion status

The goal is clear: to move CAR-T management from experience-based decision-making toward biomarker-assisted precision management.

Q2. In molecularly high-risk B-cell lymphoma, what new hope does CAR-T therapy offer, and can we assess efficacy at an earlier stage?

We observed two particularly noteworthy findings.

First, patients with TP53 mutations may still derive meaningful benefit from CAR-T therapy.
In the chemotherapy era, TP53 mutations were well established as an adverse prognostic factor and were associated with poor outcomes in diseases such as CNSL and diffuse large B-cell lymphoma (DLBCL). Our data suggest that CAR-T therapy may, to some extent, mitigate the negative prognostic impact of TP53 mutations, offering new therapeutic value for molecularly high-risk patients—although further studies are needed to refine risk stratification strategies.

Second, dynamic changes in PD-1 expression may help predict treatment trajectories at an early stage.

We found that a rising trend in PD-1 expression—from low to higher levels—may reflect more robust in vivo activation of CAR-T cells, and this dynamic pattern was associated with better clinical outcomes. This observation not only aids early efficacy assessment, but also provides a rationale for exploring combination strategies involving CAR-T therapy and PD-1 inhibitors.

Overall, CAR-T management is evolving from meticulous clinical observation alone toward precision management that integrates laboratory and molecular biomarkers.

Q3. Given the limited treatment options for CNSL, what are the latest advances in CAR-T therapy, and which factors most strongly influence efficacy?

Our prospective phase I study in CNSL was selected for oral presentation at ASH. While real-world data had previously suggested some therapeutic activity, prospective evidence remained limited. Our study provides more systematic and structured data in this field.

The results indicate that CD19 CAR-T therapy demonstrates meaningful antitumor activity in relapsed/refractory CNSL. We also found that treatment outcomes may be influenced by multiple factors, including patient age, disease stage, and pre-treatment clinical status.

One clear clinical implication is that maximal tumor burden reduction prior to CAR-T infusion—in other words, effective debulking—may be a critical prerequisite for optimizing CAR-T efficacy.

Q4. T-cell lymphoma is particularly challenging. What are the key innovations and long-term benefit signals from CD7 CAR-T therapy?

T-cell lymphoma represents one of the most challenging frontiers for CAR-T therapy. Although short-term response rates can be relatively high, achieving durable long-term benefit remains difficult. Our phase I study of CD7 CAR-T therapy highlighted three important points.

First, a broader eligible population. In addition to T-ALL/LBL, we included patients with certain subtypes of mature T-cell lymphoma, expanding the potential application boundaries of CD7 CAR-T therapy.

Second, high response rates can be achieved even with low-dose infusion. Our data showed that overall response rates exceeded 80% despite the use of low-dose CAR-T strategies, suggesting that high doses may not be necessary to achieve antitumor activity.

Third, long-term follow-up underscores the value of bridging to allogeneic transplantation. Patients who achieved durable responses or potential cure were more frequently those who subsequently underwent allogeneic hematopoietic stem cell transplantation, whereas long-term outcomes were less favorable in patients who did not proceed to transplant.

These findings suggest that when CD7 CAR-T is used as salvage therapy, early evaluation and planning for allogeneic transplantation as consolidation should be considered in eligible patients to maximize long-term benefit.

Q5. CAR-T therapy combined with transplantation: which patients may benefit most, and what are the future directions?

Combination strategies integrating CAR-T therapy and transplantation are gaining increasing attention. This year, we focused particularly on a highly challenging population: patients who fail CD19 CAR-T therapy. These patients often exhibit both chemotherapy resistance and CAR-T resistance and can be considered “double refractory,” with very limited treatment options.

Our findings suggest that if patients can still achieve some degree of response after debulking chemotherapy (including targeted combinations), consolidation strategies may be considered, such as:

• Autologous transplantation combined with CAR-T targeting alternative antigens
• Allogeneic transplantation combined with donor-derived CAR-T therapy

The overarching goal is to achieve improved disease control and more durable long-term outcomes.

In summary, the success of combination strategies depends on understanding the complementary mechanisms of CAR-T therapy and transplantation, as well as precise patient selection, ensuring that those most likely to benefit can do so from intensified therapeutic approaches.