Psoriasis Resolution in a Patient Treated With CD19 CAR T-Cell Therapy for Refractory DLBCL

Key Takeaways

Psoriasis involves keratinocyte hyperproliferation and inflammatory pathways, with emerging evidence suggesting a role for B cells in its pathogenesis.
CD19 CAR T-cell therapy, effective in relapsed/refractory DLBCL, incidentally induced psoriasis remission, highlighting potential therapeutic implications.
The case underscores the need for further research into CAR T-cell therapy's safety and efficacy in treating nonmalignant immune-mediated conditions.
Careful management of cytokine release syndrome is crucial when considering CAR T-cell therapy for immune-mediated diseases.

CD19 CAR T-cell therapy may modulate immune dysregulation in underlying diseases such as psoriasis.

Image credit: DermNet

As an immune-mediated inflammatory skin disorder, psoriasis is characterized by hyperproliferation of keratinocytes and an inflammatory cascade involving dendritic cells, T-helper 17 cells, and cytokines such as IL-17, IL-23, and TNF-α. While treatments such as biologics targeting these pathways are effective, some patients experience refractory disease.^1,2

While advances have been made in understanding the mechanisms of psoriasis, its precise etiology and pathogenesis are not yet fully understood, despite its impact on approximately 2% of the global population. Emerging research suggests that although psoriasis has been considered a largely T-cell–mediated disease, B cells may also contribute to the disease's development and progression. Particularly, CD19+ B cells and skin-associated autoreactive B cells may play a role in psoriasis pathogenesis.^3,4

Diffuse large B-cell lymphoma (DLBCL) is the most common aggressive non-Hodgkin lymphoma.⁵ Standard first-line treatment with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) achieves a cure in approximately 50% to 60% of patients, but up to 40% develop relapsed or refractory disease (R/R DLBCL). For these patients, chimeric antigen receptor (CAR) T-cell therapy targeting CD19 offers an effective second-line option, with 1-year survival rates of 48% to 83%.⁶

Emerging evidence suggests that CART-cell therapy could also influence autoimmune conditions.⁷ This case report documents a patient with R/R DLBCL and chronic psoriasis who achieved psoriasis remission following CD19 CART-cell therapy. It provides an intriguing insight into the interplay between oncologic immunotherapy and immune-mediated diseases.⁸

Case Presentation

The case involved a 65-year-old man with a 45-year history of generalized plaque psoriasis and no prior systemic immunosuppressive therapy. The patient presented with R/R DLBCL confirmed via imaging, biopsy, and immunophenotyping. Despite partial remission after R-CHOP, the lymphoma progressed. The patient then received CD19 CART-cell therapy.

Takeaway Points

Psoriasis is a chronic inflammatory skin disease primarily mediated by T cells, with emerging evidence of a role for B cells in its pathogenesis.
Chimeric antigen receptor (CAR) T-cell therapy, initially developed for hematologic malignancies, may have unexpected therapeutic effects on immune-mediated diseases such as psoriasis.
In this case, CD19 CART-cell therapy for relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) resulted in near-complete remission of long-standing plaque psoriasis.
This report highlights the potential of CD19 CART-cell therapy to target autoreactive skin-associated B cells, suggesting a novel mechanism and a promising avenue for refractory psoriasis treatment.

At baseline, psoriasis was severe with a Psoriasis Area and Severity Index (PASI) of 64.8 and Dermatology Life Quality Index (DLQI) of 20, with no improvement following rituximab-based chemotherapy. However, after initiating CART-cell infusion, skin lesions improved within 4 weeks, with a PASI score of 18.7, alongside an improvement in DLBCL symptoms. One year after CART-cell therapy, the patient maintained complete remission of DLBCL (as demonstrated by PET-CT scan) and achieved near-complete remission of psoriasis, with a decrease in his PASI score to 4.8 and DLQI to 2. This improvement persisted over the 3.5-year follow-up period without the use of additional systemic psoriasis treatments.

The patient experienced grade 1 cytokine release syndrome (CRS) following initiation of CD19 CART-cell therapy. The CRS was resolved with symptomatic management.

Clinical Implications

This case demonstrates a novel therapeutic possibility for refractory psoriasis through CD19 CART-cell therapy. Key implications include:

Targeting B Cells in Psoriasis: The patient’s remission highlights the potential role of B cells in psoriasis and suggests that CD19-targeted therapies could be effective in treating refractory cases.
Expanding CART Indications: The immunomodulatory effects of CART-cell therapy may extend beyond oncology, providing insights into treating other immune-mediated diseases.
Safety Considerations: While CRS is a common adverse event with CART-cell therapy, it must be carefully managed when considering this treatment for immune-mediated conditions.
Future Research Directions: This case underscores the need for larger studies to elucidate mechanisms and assess the safety and efficacy of CART-cell therapy in nonmalignant conditions.

Conclusion

The incidental remission of psoriasis in this case suggests a potential new avenue for treating refractory immune-mediated skin diseases. CD19 CART-cell therapy may modulate immune dysregulation in underlying diseases such as psoriasis. While promising, these findings are limited by the case report nature and warrant further investigation to validate and expand upon this therapeutic approach. Further studies are needed to explore the mechanisms behind these effects and to evaluate the safety and efficacy of CART-cell therapy for psoriasis in broader patient populations.

Jennifer Fisher, MMSc, PA-C, is a board-certified dermatology physician assistant and medical writer in Connecticut.

References

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