Hematological Oncology | Dr. Yajing Zhang and Prof. Minghui Duan: CD19 CAR-T Therapy Achieves Durable Treatment-Free Remission in a Rare Case of Castleman Disease

Idiopathic multicentric Castleman disease (iMCD) is a rare, life-threatening lymphoproliferative disorder characterized by marked clinical heterogeneity and complex immune dysregulation. Safe and effective therapies capable of producing durable remission have remained limited, making iMCD one of the most challenging immune-mediated rare diseases in clinical practice. While CAR-T cell therapy has significantly expanded beyond B-cell malignancies into immune-related disorders, its application in rare lymphoproliferative diseases such as iMCD is still in the early stages.

A new study, led by Dr. Yajing Zhang of GoBroad Healthcare Group as first author, with Prof. Minghui Duan of Peking Union Medical College Hospital as corresponding author, and Prof. Lu Zhang (Peking Union Medical College Hospital) together with Dr. Hongsheng Zhang (Fudan University/Yake Biotechnology) as co-corresponding authors, has been published in the international journal Hematological Oncology.

The report presents the world's first documented case of a patient with refractory HHV-8-negative iMCD achieving complete treatment-free remission lasting more than 12 months following CD19 CAR-T therapy. The findings also provide important clinical evidence supporting a B-cell–centric disease model, offering new insights into future therapeutic strategies for Castleman disease.

A 12-Year Journey Before a New Treatment Option

The patient was a 31-year-old woman diagnosed with HHV-8-negative iMCD (plasma cell/IPL subtype). During more than 12 years of disease, she underwent multiple lines of therapy—including COP, CHOP, thalidomide, bortezomib and sirolimus—but none achieved durable disease control.

Pathological examination demonstrated preserved lymph node architecture with the characteristic "onion-skin" appearance, while CD138 immunohistochemistry revealed diffuse plasma cell proliferation, consistent with the iMCD-IPL subtype.

Clinically, she experienced persistent systemic inflammation, including markedly elevated CRP, ESR and IL-6 levels, severe hypergammaglobulinemia (peak IgG: 68.0 g/L), generalized lymphadenopathy, splenomegaly and recurrent inflammatory symptoms. Limited efficacy and accessibility of conventional therapies, including IL-6 pathway inhibition, suggested that a more fundamental immune mechanism might be driving the disease.

Why CD19 CAR-T Was Selected

Years of unsuccessful treatment had significantly affected the patient's career, daily life and future plans.

After comprehensive discussions between the multidisciplinary team and the patient, several treatment options were carefully evaluated:

• Anti-IL-6 therapy (siltuximab), the current standard treatment requiring long-term administration;
• B-cell depletion with rituximab, which may provide benefit but often with limited durability;
• Additional chemotherapy and immunomodulatory therapies, which had already failed to achieve sustained disease control.

The patient hoped to achieve durable remission after a single treatment. Given her persistent inflammatory burden and evidence of abnormal B-cell activation, she and the medical team jointly decided to proceed with CD19 CAR-T therapy under an approved clinical study (ChiCTR1900025419).

Treatment Was Well Tolerated

Following standard lymphodepleting chemotherapy with fludarabine and cyclophosphamide (FC regimen), the patient received autologous CD19 CAR-T cells at a dose of 1 × 10⁶ CAR-positive T cells/kg.

The treatment demonstrated a favorable safety profile:

• Grade 1 cytokine release syndrome (CRS), presenting only as low-grade fever;
• No immune effector cell-associated neurotoxicity syndrome (ICANS);
• Peak CAR-T expansion occurred on Day 11 after infusion;
• B-cell depletion lasted from Day 7 to Day 198;
• No Grade 3 or higher treatment-related adverse events were observed.

Durable Remission and Improved Quality of Life

The patient experienced rapid and sustained clinical improvement following treatment.

Inflammatory markers—including CRP, ESR and IL-6—declined quickly and remained within normal ranges. Her anemia resolved progressively, immunoglobulin levels decreased as expected following CD19-positive B-cell depletion, and systemic symptoms disappeared completely.

More than 12 months after treatment, she continues to maintain complete remission without any ongoing therapy.

The sustained disease control has also transformed her quality of life. She has returned to work, resumed normal daily activities and begun planning for the future. Having regained confidence in her health, she is now preparing for pregnancy.

Immune Rebalancing Beyond B-Cell Depletion

Serial immune monitoring showed prolonged peripheral B-cell depletion that closely paralleled the patient's clinical remission.

At the same time, systemic inflammatory mediators—including CRP, ESR and IL-6—declined and stabilized, suggesting restoration of immune homeostasis.

These findings indicate that, in the plasma cell subtype of iMCD, B cells may play a central pathogenic role rather than simply participating in downstream inflammation. The results provide further support for the B-cell–centric disease model, suggesting that CD19 CAR-T therapy may achieve long-term disease control by eliminating pathogenic B-cell populations and restoring immune balance.

Expert Perspectives

Dr. Yajing Zhang commented that this case demonstrates the importance of revisiting disease classification and underlying mechanisms, even in patients with longstanding refractory Castleman disease.

"Future treatment may move beyond simply suppressing inflammation toward identifying the biological drivers of disease and restoring immune balance. Rare disease research often begins with careful observation of individual patients, opening new possibilities for understanding disease biology."

Prof. Minghui Duan noted that for patients with refractory Castleman disease, identifying the underlying immune abnormalities is critical.

"Rather than focusing solely on inflammatory pathways, future strategies should aim to restore immune homeostasis. CAR-T therapy has shown encouraging potential, although its clinical application requires careful patient selection, standardized management and long-term follow-up in experienced centers. For patients who respond poorly to conventional therapy, CAR-T offers an important direction for future clinical investigation."