Background

Primary mediastinal large B-cell lymphoma (PMBCL) is a unique subtype of lymphoma, and the optimal treatment approach remains a subject of ongoing discussion. Polatuzumab vedotin, an anti-CD79b monoclonal antibody, when combined with rituximab, cyclophosphamide, doxorubicin, and prednisone (Pola-R-CHP), offers the benefits of more convenient administration and comparable safety to the R- CHOP regimen, while demonstrating reduced toxicity comparison to DA-EPOCH-R.

Aims

To assess the clinical features and treatment trategies of PMBCL in a Chinese cohort, emphasizing the effectiveness and safety of innovative therapeutic approaches.

Methods

We retrospectively analyzed clinical data collected between December 2024 and January 2025, utilizing PET-CT to assess therapeutic response and evaluate the safety and efficacy of the treatment.

Results

A total of 22 patients were enrolled in this study, with a median age of 32.5 years (22-73). 10 were men and 12 were women, the ratio was 1: 1.2. The majority of patients (68.18%) presented with advanced- stage disease (Stage III/IV), while 59.09% exhibited mediastinal invasion without bone marrow involvement.

In the frontline therapy, 21 patients received DA-EPOCH-R. Among them,13 achieved complete metabolic response(CMR; Deauville score1-3), while 8 showed resistance(Deauville score 4-5). Notably, a 73-year-old man with stage 4B disease and an IPI 3, complicated by hepatic and renal dysfunction, left atrial enlargement, and aortic regurgitation, was treated with Pola-R- CHP as first-line therapy due to his advanced age and comorbid conditions. PET-CT imaging revealed CR, with a Deauville score of 3 after 3 cycles and a score of 2 after 6 cycles. The patient has maintained sustained CR to date.

Among the 8 resistant patients, 3 underwent salvage radiotherapy, with one CMR. Another patient attained CMR following R-ESHAP treatment for lymph node relapse, whereas one succumbed to CNS relapse despite receiving multiple therapies, including surgery, HD-MTX BV, selinexor, and thiotepa.5 patients received targeted therapies. 1 patient, who failed BV-DA-EPOCH, enrolled in a clinical trial. Another achieved CR with PD-1 inhibitor therapy.2 patients received Pola-R-CHP: one, a 27-year-old female with stage 2B disease and an IPI 3, exhibited a poor response to initial therapies(R-CHOP and DA- EPOCH-R) but achieved CR with a Deauville score of 3 after 6 cycles, including the resolution of bilateral pleural effusion after the first cycle. The second was a 32-year-old male with PMD following 7 cycles of DA-EPOCH-R and radiotherapy. He achieved sustained complete remission for over 6 months after 4 cycles of Pola-R-CHP, which served as a bridge to CAR-T therapy and autologous stem cell transplantation.

The Overall Response rate (ORR) to first line was 86.3% and responses to 2nd line were achieved in 3/7 patients. All AEs were recoverable, except for one reported death(due to disease progression).The median follow-up period was 46.97 months ranging from 14.3 to 114.43 months and the median progression-free survival(PFS) or overall survival (OS) had not been reached. Among the 3 patients treated with Pola-R-CHP, all received the full dosage, and no grade 4 myelosuppression was reported.

Summary/Conclusion

POLA-R-CHP shows potential as an efficient therapy for PMBCL. Its frontline application could enhance overall response rates while reducing treatment-related toxicity.

Keywords: Real world data, Non-Hodgkin's lymphoma

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2025
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