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地尼白介素-毒素连接物和美罗华联合治疗B细胞非霍奇金淋巴瘤的二期临床结果

资料来源于British Journal of Haematology, August 2007

原文标题： Phase II trial of the combination of denileukin diftitox and rituximab for relapsed/refractory B-cell non-Hodgkin lymphoma

Denileukin diftitox plus rituximab was evaluated in relapsed/refractory B-cell non-Hodgkin lymphoma patients. Of the 38 evaluable patients, 30 (80%) were rituximab-refractory. The overall response rate (ORR) was 32%, with six complete responses (CR) and six partial responses (PR). The median time to progression for responders was 8 months (range: 2–36+); two patients with rituximab-refractory follicular lymphoma were in CR at 25 and 36+ months. The ORR was 55% (4 CRs, 2 PRs) in 11/14 patients with rituximab-refractory follicular lymphoma, and 100% in the three patients with rituximab-sensitive tumour. Most toxicities were low grade and transient, and myelotoxicity was uncommon.

美罗华，吉西他滨，草酸铂：治疗复发/难以控制的B细胞淋巴瘤的有效补救方案

资料来源于Annals of oncology ，[2007 May 11]

原文标题： Rituximab, gemcitabine and oxaliplatin: an effective salvage regimen for patients with relapsed or refractory B-cell lymphoma not candidates for high-dose therapy.

背景：大剂量化疗联合干细胞移植是治疗复发性淋巴瘤的参考疗法，但是并不是适合所有的病人。常规的化疗补救方案效率有限并且毒副作用大。美罗华、吉西他滨和草酸铂是用来治疗复发或者难以控制的淋巴瘤病人的常用的单一药物，试验证明他们之间有协同作用。

方法：46个复发/难以控制的B细胞淋巴瘤病人接受了8个周期的R-GemO治疗(第一天：美罗华 375mg/m2，第二天：吉西他滨 1000mg/m2 草酸铂100mg/m2）。其中大部分(72％)是弥漫大B细胞淋巴瘤患者。

结果：4个R-GemO周期治疗后，ORR是83％(50% CR) 。在之前接受过美罗华治疗的病人种，8个疗程后CR/CRu 是65％。2年无事件生存率是43％，总体生存率（28个月）为66％。在有反应的病人当中，2年无疾病的概率是62％。治疗中的毒副作用是可以忍受的。

结论：对于不能接受HDT的复发/难以控制的B细胞淋巴瘤患者，R-GemOx方案治疗效果明显，副作用可以接受。

BACKGROUND: High-dose therapy (HDT) with stem-cell support is the reference treatment for relapsed lymphoma, but is not appropriate for all patients. Conventional salvage chemotherapies have been used with limited efficacy and significant toxicity. Rituximab, gemcitabine and oxaliplatin are active as single agents in relapsed or refractory lymphoma, and have demonstrated synergistic effects in vitro and in vivo.

PATIENTS AND METHODS: Forty-six patients with relapsed or refractory B-cell lymphoma received up to eight cycles of R-GemOx (rituximab 375 mg/m(2) on day 1, gemcitabine 1000 mg/m(2) and oxaliplatin 100 mg/m(2) on day 2). The majority (72%) had diffuse large B-cell lymphoma.

RESULTS: After four cycles of R-GemOx, the overall response rate was 83% [50% complete response (CR)/unconfirmed CR (CRu)]. High CR/CRu rates were observed in all histological subtypes. In patients who had previously received rituximab, the CR/CRu rate after eight cycles was 65%. The 2-year event-free and overall survival rates (median follow-up of 28 months) were 43% and 66%, respectively. Among responders, the probability of being disease free for 2 years was 62%. Treatment was generally well tolerated.

CONCLUSION: R-GemOx shows promising activity with acceptable toxicity in patients with relapsed/refractory B-cell lymphoma who are not eligible for HDT.

galiximab抗体（CD80抗体）联合美罗华治疗复发/难以控制的滤泡型淋巴瘤的I/II期临床结果

资料来源于Annals of oncology

原文标题：A phase I/II study of galiximab (an anti-CD80 monoclonal antibody) in combination with rituximab for relapsed or refractory, follicular lymphoma

Background: Galiximab is a monoclonal antibody that targets CD80, a costimulatory molecule constitutively expressed on follicular and other lymphomas. Modest single-agent clinical activity and tolerability were
demonstrated in a phase I study in relapsed or refractory, follicular non-Hodgkin' s lymphoma (NHL). A phase I/II study was conducted to evaluate galiximab in combination with a standard course of rituximab. Safety,
pharmacokinetics, and efficacy were evaluated.

Patients and methods: Patients with follicular NHL who had relapsed or failed primary therapy were enrolled. Rituximab-refractor y patients (no response or a response with time to progression <6 months) were excluded. Patients received 4 weekly i.v. infusions of galiximab (125, 250, 375, or 500 mg/m2) and rituximab (375 mg/m2). International Workshop Response Criteria (IWRC) were used to evaluate response.

Results: Seventy-three patients received treatment. All had received at least one prior lymphoma therapy; 40% were rituximab naive. Infusions were delivered in an outpatient setting and were well tolerated. The most common study-related adverse events (AE) were lymphopenia, leukopenia, neutropenia, fatigue, and chills. The overall response rate at the recommended phase II dose of galiximab (500 mg/m2) was 66%: 19% complete response, 14% unconfirmed complete response, and 33% partial response. The median progression free survival was 12.1 months. Combination therapy did not appear to alter pharmacokinetics.

Conclusion: These results indicate that galiximab can be safely combined with a standard course of rituximab. This doublet biologic approach offers the potential to avoid or delay chemotherapy or to integrate with other lymphoma therapies. A phase III, randomized study evaluating clinical benefit of rituximab versus the combination has been initiated.