New Effective Treatment of Primary Mediastinal B cell Lymphoma in

Taiwan: A Single Institution Experience

Miao-Erh Chang, Jyh-Pyng Gau, Hao-Yuan Wang, Po-Shen Ko, Yao-Chung Liu, Liang-Tsai Hsiao, Tzeon-Jye Chiou, Po-Min Chen, Jin-Hwang Liu

Taipei Veterans General Hospital

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INTRODUCTION

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• Primary mediastinal B cell lymphoma (PMBCL)

– derives from putative thymic B cells

– about 10% of diffuse large B cell lymphomas (DLBCL)

– women in 30s~40s

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Blood 2015 125:33-39

• Clinical features

– a bulky tumor in the anterior mediastinum

– local compressive symptoms (50%): dyspnea, cough, dysphagia, a superior vena cava syndrome

– pleural or pericardial effusions, often present

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The Oncologist May 1, 2006 vol. 11 no. 5 488-495

• PMBCL, an aggressive lymphoma, favorable outcomes compared to other subgroups of DLBCL (activated B cell subtype)

• NO large prospective randomized studies for therapy of PMBCL, a lack of treatment standards

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• Standard-dose chemoimmunotherapy needs consolidative mediastinal radiotherapy to cure the disease

• Aggressive chemoimmunotherapy, greatly improve outcomes, obviate radiotherapy, infusional dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, rituximab (DA-EPOCH-R)

• Caucasian population Asian population

Dunleavy K, et al. Dose-adjusted EPOCH-rituximab therapy in primary

mediastinal B-cell lymphoma. NEJM; 2013; 368:1408-1416

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METHODS

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Patients

• 2013/8 ~ 2016/10

• 12 patients, newly-diagnosed PMBCL, infusional DA-EPOCH-R, in Taipei Veterans General Hospital

• Primary study objectives: event-free survival (EFS) rate and overall survival (OS) rate

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Study Therapy• Infusional DA-EPOCH-R for 6-8 cycles

• Evaluation of diseases after cycle 3-4 and 6

• DA-EPOCH-R Regimen

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N Engl J Med 2013; 368:1408-1416

Study Therapy

• Revised Response Criteria for Malignant Lymphoma by International Working Group

• All patients, evaluated by FDG-PET-CT after therapy

• Tumor biopsy as clinically indicated

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RESULTS

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Baseline characteristics

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Clinical Outcomes• Median follow-up: 22.3 months (9.7~38.1)

• EFS rate: 92% (95% CI, 76-100%)

• OS rate: 100%

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Clinical Outcomes

• After treatment

– 1 patient, pathology-confirmed residual disease

• 3 cycles of R-ESHAP + mediastinal radiotherapy PD

• Auto-HSCT conditioned with BEAM CR

• Allo-HSCT with RIC (fludarabine + busulfan) CR

– 1 patient, a suspicious residual tumor

(no tumor biopsy)

• prophylactic mediastinal radiotherapy CR

• At the last follow-up, 2 patients remaineddisease-free

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FDG-PET-CT Findings

Scores of 1 and 2 “negative”Scores of 4 and 5 “positive”Score 3 according to the clinical condition

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Dose and Toxicity of DA-EPOCH-R

• Mean cumulative dose of doxorubicin: 297 mg/m2

(241-388) NO cardiac complication

• All patients, A dose escalation

• 58% to dose level 3

• 17% to dose level 4

16N Engl J Med 2013; 368:1408-1416

Dose and Toxicity of DA-EPOCH-R

• Absolute neutrophil count (ANC) nadirs

– 100~499/mm3 30% of cycles (74)

– <100/mm3 12% of cycles

• Platelet count < 30,000/mm3 0% of cycles

• Blood transfusion 0% of cycles

• Hospitalization for neutropenic fever 8% of cycles

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CONCLUSION

• Infusional DA-EPOCH-R in PMBCL offers excellent outcomes and obviates the need for radiotherapy in Asian population.

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