丨 CTI 2025 International Cell & Immunotherapy Congress

To promote innovation in China’s cell and immunotherapy landscape, facilitate in-depth exchange on key scientific questions, share the latest clinical research progress, and strengthen global collaboration and clinical translation, the 2025 International Cell & Immunotherapy Congress (CTI 2025)—jointly organized by Zhejiang University, the International Academy for Clinical Hematology (IACH), the Zhejiang Society of Immunology, and the Zhejiang Anti-Cancer Association, and co-hosted by the First Affiliated Hospital of Zhejiang University School of Medicine and the Liangzhu Laboratory—was held in Hangzhou from November 13 to 16, 2025.

During the meeting, Oncology Frontier – Hematology News invited Prof. Chunrui Li from Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, to discuss key topics surrounding CAR-T therapy for multiple myeloma—including advances in targets, breakthroughs in clinical data, translational challenges, and evolving treatment positioning—with the aim of providing forward-looking insights and valuable experience for the field.

Q1 What are the current directions of progress in CAR-T therapy for multiple myeloma? How do these innovations improve tumor-killing specificity and durability of response?

Prof. Chunrui Li: Indeed, CAR-T therapy for multiple myeloma has entered a true “post-BCMA era.” From the initial single-target BCMA CAR-T to today’s exploration of multi-target constructs, armored CAR-T, universal CAR-T, and in-vivo CAR-T manufacturing, the pace of technological evolution has far exceeded expectations.

The first direction is the expansion and combination of targets.

BCMA remains the central target, but clinical observations show that some patients develop antigen downregulation or antigen loss, leading to relapse. This has prompted the development of multi-target CAR-T designs, such as BCMA+GPRC5D, BCMA+CD19, or BCMA+FcRH5. Among these, GPRC5D is one of the most promising new targets. It is highly expressed on myeloma cells and minimally expressed in normal tissues. Data presented at the 2024 ASCO and EHA meetings showed that even in patients who had failed BCMA CAR-T therapy, GPRC5D CAR-T achieved an overall response rate (ORR) of about 85%, with complete response rates exceeding 70%, and a median progression-free survival (PFS) of more than one year. This demonstrates a new path to overcoming antigen escape.

The second direction is CAR structural optimization and enhancement of cellular function.

Traditional CARs mainly use CD28 or 4-1BB costimulatory domains, while next-generation designs introduce cytokine autocrine modules such as IL-7, IL-15, or CCL19 to improve CAR-T homing and persistence. At the same time, manufacturing processes now emphasize preservation of the stem-cell memory T-cell (Tscm) subset, which supports long-term immune surveillance. A 2024 Nature Medicine study showed that CAR-T products with a high proportion of Tscm achieved approximately a 30% improvement in response durability at 12 months, underscoring the importance of this strategy.

The third direction is universalization and controllability.

Universal or allogeneic CAR-T products remove TCR and HLA molecules via gene editing, greatly reducing the risk of GVHD and enabling “off-the-shelf” treatment. Although host immune rejection remains a challenge, early clinical results suggest feasibility. At the same time, “switchable CAR-T” designs allow activity to be regulated by small-molecule drugs, balancing efficacy and safety. There is also ongoing exploration of in-vivo CAR-T technology. For example, at our center, a proof-of-concept evaluation in five patients achieved an ORR of 100%, and many companies worldwide are actively developing in-vivo CAR-T platforms.

Overall, next-generation CAR-T therapies are achieving greater precision in tumor targeting, broader antigen coverage, and structural breakthroughs in persistence and safety. The shift from “aggressive killing” to “precise and durable immunity” marks a critical leap in the evolution of immunotherapy for multiple myeloma.

Q2 What clinical breakthroughs have emerged in recent years? Are the therapeutic outcomes consistent in high-risk groups such as the elderly, heavily pretreated patients, or those with relapse?

Prof. Chunrui Li: CAR-T therapy has fundamentally changed the natural course of multiple myeloma. We are no longer asking only whether it works, but whether it can achieve long-term control—or even functional cure.

Looking first at overall efficacy: For example, with the BCMA-targeted product Cilta-cel, five-year follow-up data from the CARTITUDE-1 study showed that about one-third of patients remained progression-free five years after a single infusion—an unprecedented milestone in the history of multiple myeloma. In early-relapse disease, the CARTITUDE-4 trial further confirmed that Cilta-cel reduced the risk of disease progression by 74% compared with standard therapy and achieved, for the first time, a statistically significant overall survival (OS) benefit. This marks the transition of CAR-T therapy from last-line rescue to early intervention.

Next is the stability of efficacy in high-risk populations. For elderly patients, age ≥70 is not a contraindication. Multiple real-world studies show that their PFS and incidence of cytokine release syndrome (CRS) are comparable to those of younger patients, provided that patient selection is precise and supportive care optimized. Among patients with complex cytogenetics (such as del17p or t(4;14)) or extramedullary disease, Cilta-cel still offers clear advantages over traditional treatments. In heavily pretreated patients or those who relapse after BCMA exposure, GPRC5D-targeted CAR-T therapy yields response rates exceeding 70%, offering renewed hope for the most difficult-to-treat groups.

Even more inspiring is the emergence of a “curative plateau.”

In the long-term follow-up of CARTITUDE-1, the survival curve showed the first signs of flattening, suggesting that some patients may achieve long-term disease control or functional cure. This “single infusion, long remission” paradigm is reshaping the treatment logic for multiple myeloma. Across elderly, relapsed, and heavily pretreated populations, CAR-T therapy is delivering deep, durable responses and transitioning from a “life-saving weapon” to a “core therapeutic option.”

Q3 What are the key challenges for the clinical translation of next-generation CAR-T therapy? How is its therapeutic positioning evolving in the treatment of multiple myeloma?

Prof. Chunrui Li: The success of CAR-T therapy is remarkable, but broad clinical implementation still faces three major challenges: manufacturing accessibility, relapse and resistance, and safety oversight.

First, accessibility and manufacturing time. Autologous CAR-T typically requires 4–6 weeks from cell collection to infusion, which some late-stage patients simply cannot wait for. Meanwhile, high costs and limited treatment capacity restrict availability. Current solutions include rapid-manufacturing platforms such as FasTCAR, which can shorten production time to under 30 hours; allogeneic CAR-T using healthy donor cells to create “off-the-shelf” products; and in-vivo CAR-T, which uses mRNA or LNPs to engineer CAR-T cells directly inside the patient—considered by many as the ultimate future direction, although further validation is needed.

Second, relapse and resistance. The main mechanisms include BCMA loss (antigen-negative relapse) and T-cell exhaustion (antigen-positive relapse). Multi-target and armored CAR-T designs are emerging to address these challenges. Multi-target constructs counter antigen escape, while armored CAR-T secreting IL-15 or resisting TGF-β signaling helps maintain T-cell fitness. These innovations are gradually reducing relapse rates and prolonging remission duration.

Third, safety and regulatory oversight. In 2024, the FDA required all BCMA and CD19 CAR-T products to carry a boxed warning regarding the potential risk of secondary T-cell malignancies. However, large real-world studies show an extremely low incidence (<0.2%). This highlights the importance of rational risk assessment, long-term monitoring, and robust data registries. For new targets such as GPRC5D, clinicians must also be aware of characteristic skin, oral, and nail-related adverse events—typically manageable but requiring clinical experience.

Regarding treatment positioning, CAR-T therapy has made a historic shift earlier in the treatment pathway. The KarMMa-3 and CARTITUDE-4 studies confirmed its superiority in early-relapse settings. In 2024, the FDA approved Cilta-cel for lenalidomide-refractory patients at first relapse. The ongoing CARTITUDE-6 trial will directly compare CAR-T with autologous stem cell transplantation (ASCT) in frontline therapy. If positive, CAR-T could potentially replace ASCT as the standard treatment for high-risk newly diagnosed patients.

Overall, CAR-T is transitioning from “end-stage salvage therapy” to a “main therapeutic modality,” with continual breakthroughs in technology, strategy, and accessibility. It represents not only a therapeutic upgrade but also the accelerating arrival of an era in which multiple myeloma becomes a disease that is controllable—and possibly curable.

In summary, CAR-T therapy for multiple myeloma is undergoing a transformative shift from target innovation to extended efficacy and earlier clinical application. The key question moving forward is no longer whether CAR-T works, but rather how to ensure that more patients can access it earlier and more safely.

Expert Biography

Prof. Chunrui Li

• Professor of Medicine, Chief Physician

• Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology

• Master’s and PhD Supervisor

• Specializes in immunotherapy for plasma cell disorders and hematologic malignancies

• Member, Myeloma Group, Chinese Medical Association Hematology Branch

• Standing Member, Hematology Branch, Hubei Medical Association

• Chair, Hematology Committee (Hubei), Chinese Society of Gerontology & Geriatrics

• CGP Inspector, Hubei Province

• Standing Member, 1st CSCO Myeloma Expert Committee

• Led the approval of China’s first BCMA-targeted CAR-T product (Iquilunsai Injection)

• Presenter at ASH, EHA, ASCO, IMW and other international congresses

• Executive Editorial Board Member, Journal of Critical Care Internal Medicine

• PI of multiple National Natural Science Foundation projects

• First or corresponding author of >30 SCI papers, including JAMA Oncology and Blood