NEJM：利妥昔单抗方案治疗纵隔B细胞淋巴瘤可避免放疗

发表于2013年4月最新一期NEJM期刊上的一项研究显示，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。

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。美国国立癌症研究所(NCI)的Kieron Dunleavy博士及其同事称：“上述结果表明，DA-EPOCH-R方案是此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且带瘤时间超过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。Dunleavy博士及其同事等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。

与淋巴瘤相关的拓展阅读：

• JCO:ABVD标准治疗方案不适用于老年霍奇金淋巴瘤
• Blood：红斑狼疮治疗药不增加淋巴瘤风险
• NEJM：霍奇金淋巴瘤患儿药物短缺不容小觑
• Mol Cell Biol：鉴别淋巴瘤突变的好坏
• Cancer Discovery：Everolimus 可用于治疗Myc驱动的淋巴瘤
• 疟疾患者得Burkitt淋巴瘤风险增高
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Dose-adjusted EPOCH-rituximab therapy in primary mediastinal B-cell lymphoma
Background
Primary mediastinal B-cell lymphoma is a distinct subtype of diffuse large-B-cell lymphoma that is closely related to nodular sclerosing Hodgkin's lymphoma. Patients are usually young and present with large mediastinal masses. There is no standard treatment, but the inadequacy of immunochemotherapy alone has resulted in routine consolidation with mediastinal radiotherapy, which has potentially serious late effects. We aimed to develop a strategy that improves the rate of cure and obviates the need for radiotherapy.
Methods
We conducted a single-group, phase 2, prospective study of infusional dose-adjusted etoposide, doxorubicin, and cyclophosphamide with vincristine, prednisone, and rituximab (DA-EPOCH-R) and filgrastim without radiotherapy in 51 patients with untreated primary mediastinal B-cell lymphoma. We used results from a retrospective study of DA-EPOCH-R from another center to independently verify the outcomes.
Results
The patients had a median age of 30 years (range, 19 to 52) and a median tumor diameter of 11 cm; 59% were women. During a median of 5 years of follow-up, the event-free survival rate was 93%, and the overall survival rate was 97%. Among the 16 patients who were involved in the retrospective analysis at another center, over a median of 3 years of follow-up, the event-free survival rate was 100%, and no patients received radiotherapy. No late morbidity or cardiac toxic effects were found in any patients. After follow-up ranging from 10 months to 14 years, all but 2 of the 51 patients (4%) who received DA-EPOCH-R alone were in complete remission. The 2 remaining patients received radiotherapy and were disease-free at follow-up.
Conclusions
Therapy with DA-EPOCH-R obviated the need for radiotherapy in patients with primary mediastinal B-cell lymphoma. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT00001337.)