International Journal Publication | Dr. Yajing Zhang & Prof. Minghui Duan: First Global Report of Durable Treatment-Free Remission in Castleman Disease After CD19 CAR-T Therapy

Summary: A collaborative study led by Dr. Yajing Zhang of Beijing GoBroad Boren Hospital and Prof. Minghui Duan of Peking Union Medical College Hospital was published in Hematological Oncology. It is the first systematic report worldwide of a patient with refractory HHV-8-negative idiopathic multicentric Castleman disease (iMCD) achieving complete, treatment-free remission for more than 12 months after CD19 CAR-T cell therapy. The patient had lived with the disease for over 12 years and had not achieved durable disease control despite multiple prior treatments, including COP and CHOP. After CAR-T therapy, she experienced only grade 1 cytokine release syndrome (CRS), presenting as a low-grade fever, and no immune effector cell-associated neurotoxicity syndrome (ICANS). She was able to return to normal daily life and began planning for pregnancy. Mechanistically, the case provides important clinical evidence supporting a B-cell-centric model of disease in refractory iMCD.

Idiopathic multicentric Castleman disease (iMCD) is a rare, potentially life-threatening lymphoproliferative disorder characterized by marked clinical heterogeneity and complex immune dysregulation. Safe and effective therapies capable of producing durable remission remain limited, making iMCD a particularly challenging immune-mediated rare disease. In recent years, the use of CAR-T cell therapy has expanded beyond B-cell malignancies into immune-mediated diseases, but clinical exploration in rare lymphoproliferative disorders such as iMCD is still at an early stage.

Recently, a collaborative study was published in the international journal Hematological Oncology, with Dr. Yajing Zhang of Beijing GoBroad Boren Hospital as first author, Prof. Minghui Duan of Peking Union Medical College Hospital as corresponding author, and Prof. Lu Zhang of Peking Union Medical College Hospital and Dr. Hongsheng Zhang of Fudan University/Yake Biotechnology as co-corresponding authors. The study is the first systematic report worldwide of a patient with refractory HHV-8-negative iMCD achieving complete, treatment-free remission lasting more than 12 months after CD19 CAR-T cell therapy. It also provides important clinical evidence supporting a “B-cell-centric model” of disease and offers new insights into potential treatment strategies for Castleman disease.

Case Overview

1. Twelve Years Without Durable Disease Control: A New Treatment Approach for Long-Standing Refractory iMCD

The study reports a 31-year-old woman diagnosed with HHV-8-negative iMCD with the idiopathic plasmacytic lymphadenopathy (IPL) subtype. Her disease course had lasted more than 12 years. She had previously received multiple lines of therapy, including COP, CHOP, thalidomide, bortezomib, and sirolimus, but none achieved sustained disease control.

Figure 1. Lymph Node Histopathology and Immunohistochemistry

H&E staining showed largely preserved lymph node architecture with the characteristic “onion-skin” appearance caused by concentric expansion of the mantle zones. CD138 immunohistochemistry showed extensive diffuse plasma cell proliferation in the interfollicular areas, consistent with the iMCD-IPL phenotype.

The patient had persistent systemic inflammation, with markedly elevated CRP, ESR, and IL-6; hypergammaglobulinemia, with IgG peaking at 68.0 g/L; generalized lymphadenopathy and splenomegaly; and recurrent systemic inflammatory symptoms. With standard treatments and anti-IL-6 pathway therapy either providing limited benefit or being unavailable, her disease remained chronically active, suggesting that a more upstream abnormality in immune regulation might be driving the condition.

2. A Shared Decision: Why CD19 CAR-T?

Years of repeated treatment had failed to bring the disease under lasting control and had taken a major toll on the young woman's work, daily life, and future plans. After carefully reviewing her treatment history and weighing potential benefits and risks, the medical team discussed several possible treatment paths with her.

Options included IL-6-targeted therapy with siltuximab, the current standard treatment for iMCD but one that typically requires ongoing administration; B-cell-depleting therapy with rituximab, which targets B cells but may have limitations in the depth and durability of response; and additional chemotherapy or immunomodulatory regimens, several of which she had already received with limited disease control.

The patient hoped for an approach that might offer long-term treatment-free remission after a single course of therapy. Given her longstanding inflammatory burden and evidence of abnormal B-cell activation, she and the medical team ultimately made a shared decision to proceed with CD19 CAR-T cell therapy. She provided informed consent under clinical study ChiCTR1900025419.

3. Treatment Course: Robust CAR-T Expansion With a Favorable Safety Profile

After standard lymphodepleting chemotherapy with fludarabine and cyclophosphamide (FC), the patient received an infusion of autologous CD19 CAR-T cells at a dose of 1 × 10^6 CAR+ T cells/kg. She developed grade 1 cytokine release syndrome (CRS), consisting only of a low-grade fever, which resolved with supportive care. No ICANS occurred. CAR-T cell expansion peaked on day 11 after infusion, while B-cell depletion persisted from day 7 through day 198. Overall, treatment was well tolerated, with no grade 3 or higher adverse events observed.

 Figure 2. Comprehensive Assessment of Response to CD19 CAR-T Therapy in iMCD

(A) Body temperature monitoring showed a brief low-grade fever, with a maximum temperature of 38.2°C.

(B-C) Expansion and persistence of CD19 CAR-T cells in peripheral blood, detectable from day 11 through day 58 after infusion.

(D) Changes in peripheral blood CD19+ lymphocyte counts before and after treatment.

(E) Serial changes in inflammatory markers, including CRP, ESR, and IL-6, from baseline through post-treatment follow-up.

(F) Changes in hemoglobin levels over time, showing gradual recovery after treatment.

(G) Changes in serum immunoglobulin levels (IgG, IgA, and IgM) at different time points.

4. Durable Remission and a Return to Life: Disease Control Alongside Improved Quality of Life

After treatment, the patient showed rapid and sustained systemic improvement. Inflammatory markers, including CRP, ESR, and IL-6, fell quickly and remained within the normal range over time. Her anemia improved substantially, her blood counts gradually recovered, and immunoglobulin levels decreased as expected following CD19-directed B-cell depletion. Her systemic symptoms resolved completely.

At more than 12 months of follow-up, the patient remained in complete remission without further treatment. Just as importantly, sustained disease control translated into a meaningful improvement in her quality of life. She returned to normal work and everyday activities, began making plans for the future again, and is now preparing for pregnancy. After years of chronic inflammation, repeated treatment, and restrictions on daily life, she has regained confidence in what lies ahead.

5. Mechanistic Insights: From B-Cell Depletion to Restoration of Immune Homeostasis

Serial immune monitoring showed that CD19 CAR-T therapy induced sustained depletion of peripheral B cells, closely paralleling the patient's clinical remission. At the same time, systemic inflammatory markers, including CRP, ESR, and IL-6, fell in a coordinated pattern and approached normal levels, suggesting a broader resetting of the inflammatory cascade toward immune homeostasis.

These findings suggest that, in the iMCD-IPL subtype, B cells may be more than downstream participants in inflammation and may play an important role in regulating inflammatory pathways such as IL-6. The observation further supports a B-cell-centric model of disease and suggests that CD19 CAR-T therapy may help restore immune homeostasis by systematically eliminating abnormal B-cell populations, potentially contributing to durable disease control.

Expert Commentary: One Case, One New Possibility

As CAR-T cell therapy expands from hematologic malignancies into immune dysregulation and rare diseases, mechanism-driven treatment is beginning to reshape how complex immune-mediated disorders are approached. This study represents an important step in exploring CAR-T therapy for rare inflammatory disorders such as Castleman disease.

Dr. Yajing Zhang noted that, from a patient's perspective, the key message from this case is that even when Castleman disease has remained difficult to control for years and repeated treatments have provided limited benefit, it may still be worthwhile to revisit the diagnosis, disease subtype, and underlying mechanisms. For clinicians, the case suggests that future treatment may need to move beyond simply “controlling inflammation” toward identifying the mechanisms driving disease and restoring immune balance. This is one of the most important roles of rare-disease research: learning deeply from an individual patient to uncover new possibilities and advance our understanding of the disease itself. The value of treatment is also not measured only by normalized laboratory results, but by whether a patient can return to work and everyday life, reconnect with family and society, and regain the confidence to plan for the future. For younger patients in particular, being able to return to life, make plans for a family, and look ahead again may be among the most meaningful outcomes treatment can offer.

Prof. Minghui Duan noted that, for some patients with refractory Castleman disease, the key may be to identify deeper abnormalities within the immune system rather than focusing only on suppressing visible inflammatory manifestations. This suggests that future treatment may need to go beyond blocking inflammatory pathways and explore ways to restore immune balance. CAR-T therapy has shown potential in this setting, but its clinical use still requires rigorous patient assessment, standardized management, and long-term follow-up by experienced teams. For patients with recurrent disease or limited response to conventional therapies, CAR-T may offer an important direction for further exploration. Future clinical practice will need to account for disease subtype and individual patient differences while continuing to refine treatment strategies based on a deeper understanding of disease mechanisms. The change seen in this young patient—from years of repeated treatment to returning to work and daily life—not only reflects durable disease control, but also highlights the potential of precision immunotherapy to improve quality of life.