利妥昔单抗可使纵隔B细胞淋巴瘤患者免于放疗

美国国立癌症研究所(NCI)的一项研究显示，原发性纵隔B细胞淋巴瘤联合化疗方案中添加利妥昔单抗，可获得较高的治愈率，并且还可避免胸部放疗(N. Engl. J. Med. 2013;368:1408-16 [doi:10.1056/NEJMoa1214561])。

在这项单组前瞻性Ⅱ期研究中，51例淋巴瘤成人患者接受剂量调整的依托泊苷、阿霉素、环磷酰胺、长春新碱、泼尼松和利妥昔单抗(DA-EPOCH-R)治疗。结果显示，除2例患者外，其余均免于放疗。在中位随访5年期间，无病例复发。

Kieron Dunleavy博士及其同事称：“上述结果表明，DA-EPOCH-R方案是这类淋巴瘤治疗方面的进步。”

研究者曾发现，DA-EPOCH方案总生存率为79%。为考察添加利妥昔单抗能否进一步改善治疗结局，他们纳入了肿瘤≥5 cm且带瘤时间>13年的初治患者。受试者中位年龄30岁(19~52岁)，59%为女性。纵隔B细胞淋巴瘤为晚期，中位直径11 cm。大约30%的患者属于Ⅳ期。

这51例患者均接受了6~8个周期的DA-EPOCH-R方案治疗。治疗后，2例患者病灶持续，1例患者疾病进展，其中2例患者接受纵隔放疗，1例接受切除活检，3例患者治疗后均无病生存。

随访(3~156个月)结束后，总生存率为97%，无事件生存率为93%，未见癌症复发病例。

研究者指出，原发性纵隔B细胞淋巴瘤发生于胸腺，具有侵袭性，通常表现为局部较大的纵隔肿瘤，常伴有胸腔和心包积液，患者多为年期女性。有关该疾病的研究较少，且结果不一致，因此目前尚无治疗标准。免疫化疗通常达不到肿瘤控制目标，现行治疗方案是在高强度化疗后行纵隔放疗(与严重后期副作用有关)。

该化疗方案的毒性反应与其他既往报告事件相似。中性粒细胞减少症出现于全部化疗周期的半程，血小板减少症发生率为6%，因发热和中性粒细胞减少症需要住院治疗发生率为13%。未见明显心脏毒性反应。

研究者还报告了另外一项有关DA-EPOCH-R治疗的回顾性队列研究结果。该研究纳入过去5年在斯坦福大学加州分校医学中心接受治疗的16例患者。所有患者均可免于放疗，无事件生存率为100%。

一项针对原发性纵隔B细胞淋巴瘤儿童或青少年患者DA-EPOCH-R方案治疗的国际试验正在进行中(clinical trial number NCT01516567)。

该研究由NCI资助。安进公司提供非格司亭，但没有参与研究设计、数据收集或分析。研究报告无相关利益冲突。

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By: MARY ANN MOON, Oncology Practice

Adding rituximab to combination chemotherapy for primary mediastinal B-cell lymphoma yields a high cure rate and may obviate thoracic radiation therapy, a study has shown.

Patients in a single-group, prospective phase II study were treated with dose-adjusted etoposide, doxorubicin, cyclophosphamide with vincristine, prednisone, and rituximab (DA-EPOCH-R). All but 2 of the 51 adults with lymphoma in the study were able to forgo radiotherapy, and there were no recurrences during a median follow-up of 5 years, reported Dr. Kieron Dunleavy of the National Cancer Institute and his colleagues.

"These findings suggest that DA-EPOCH-R is a therapeutic advance for this type of lymphoma," they wrote (N. Engl. J. Med. 2013;368:1408-16 [doi:10.1056/NEJMoa1214561]).

In a previous study, Dr. Dunleavy and his colleagues found that DA-EPOCH yielded an overall survival of 79%. To examine whether the addition of rituximab would further improve outcomes, they enrolled treatment-naive patients who had masses of at least 5 cm and presented over a 13-year period.

The study patients’ median age was 30 years (range, 19-52 years), and 59% were women. Mediastinal B-cell lymphoma was advanced, with a median tumor diameter of 11 cm. Approximately 30% of patients had stage IV disease.

All 51 patients received six to eight cycles of DA-EPOCH-R. Two patients showed persistent focal disease after therapy, and one patient showed disease progression. Two of the patients then underwent mediastinal radiotherapy, and one underwent excisional biopsy. All three were disease free thereafter.

After follow-up, ranging from 3 to 156 months, overall survival was 97% and event-free survival was 93%, with no recurrences of the cancer, the investigators reported.

Primary mediastinal B-cell lymphoma develops in the thymus, "predominantly affects young women, is aggressive, and typically is manifested by a localized, bulky mediastinal mass, often with pleural and pericardial effusions," they noted. There have been few prospective studies of the disease; and the findings have been conflicting, so at present there are no treatment standards. Immunochemotherapy usually does not achieve tumor control. Mediastinal radiotherapy (associated with severe late adverse effects) after aggressive chemotherapy is the current regimen.

The toxic effects of the chemotherapy regimen were similar to other previously reported events. Neutropenia occurred during half of the chemotherapy cycles overall, thrombocytopenia occurred in 6%, and hospitalization was required for fever and neutropenia in 13% of the cycles. There were no significant cardiac toxic effects.

Dr. Dunleavy and his associates also reported the results of DA-EPOCH-R therapy in an independent retrospective cohort of 16 patients treated at Stanford (Calif.) University Medical Center during the past 5 years. All of the Stanford patients were able to forgo radiation therapy, and event-free survival was 100%.

An international trial of DA-EPOCH-R for treating children or adolescents with primary mediastinal B-cell lymphoma is currently underway (clinical trial number NCT01516567).

The study was supported by the National Cancer Institute. Amgen provided filgrastim for the study but had no involvement with study design or with data collection or analysis. The investigators reported having no relevant financial conflicts.