Clinical Outcome of Dose-Adjusted R-Epoch in Frontline Therapy of Primary Mediastinal B-Cell Lymphoma in Hospital Melaka

Abstract

Background: Primary mediastinal B-cell lymphoma (PMBCL) is a unique and uncommon form of aggressive NHL that is potentially curable with combination chemotherapy and radiation therapy. A phase II study from the National Cancer Institute (NCI) demonstrated the effectiveness of a chemotherapy alone approach using the dose-adjusted DA-R-EPOCH (rituximab, etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin) regimen in the treatment of PMBCL. Given the excellent outcomes seen in this study, many hematologists adopted this regimen without consolidative radiation therapy as a front-line option for PMBCL. Aim: In our case series, we evaluate the outcomes by frontline regimen DA-R-EPOCH for the treatment of PMBCL as well as the treatment-related complications. Methods: We reported a cohort of 3 primary mediastinal large B-cell lymphoma (PMLBL) patients who had completed 8 cycles of DA-R-EPOCH by February 2018 in Hospital Melaka, Malaysia. Results: These 3 PMBCL patients were diagnosed in 2017 and all had bulky disease (>10 cm). DA-R-EPOCH treatment with an escalation dose of level 3, representing a 144% of the starting dose, were given and 40 mg of doxorubicin per square meter of body surface area were received for at least 1 cycle. Cumulative doses of anthracycline were range from 416 to 424 mg per square meter; which falls between the range in other reported studies. The 3 patients in our cohort were able to achieve partial response (PR) at the end of treatment. The average of mediastinal residual disease size was 7.13 cm. All the patients had been scheduled for radiotherapy consolidation. Hospitalization due to treatment-related complications was reported for 2 patients. One of the patients admitted to ICU due to infected chemoport. Another patient reported acquired Varicella zoster virus during the chemotherapy. He also had sinus tachycardia probably related to anthracycline with prolonged QTC and was able to be controlled by tablet carvedilol during treatment. Toxicity was assessed during administration of all the cycles of DA-R-EPOCH. Absolute neutrophil counts of less than 500 cells per cubic milliliter occurred in 30% of the cycles compared with the reported 50% in other study. The use of neutrophil-based dose adjustment maximized the delivered dose and limited the incidence of febrile neutropenia to 26% of the total cycles. Conclusion: PMBCL is a potential curable disease with combination of chemotherapy. There is no established standard treatment of PMBCL although R-CHOP chemotherapy has become a de facto standard. In fact, DA-R-EPOCH are getting more popular among treating hematologists. Our results indicated that PMBCL patients on DA-R-EPOCH regimen had a partial response and may not necessary obviate the need for radiotherapy. This is a preliminary result as 4 more patients are ongoing DA-R-EPOCH treatment.