苯达莫司汀-利妥昔单抗可使惰性淋巴瘤无进展生存期翻番

芝加哥(EGMN)——根据StiL NHL1研究的最新结果，在惰性和套细胞淋巴瘤的治疗上，苯达莫司汀-利妥昔单抗继续保持对CHOP-利妥昔单抗的优势。德国Giessen 大学医院的Mathias J. Rummel博士在美国临床肿瘤学会(ASCO)年会期间的新闻发布会上指出，鉴于苯达莫司汀-利妥昔单抗方案可使无进展生存期增加1倍且相关毒性发生率显著降低，应考虑将该方案作为这类患者的首选一线治疗。

StiL NHL1是在德国开展的一项大规模随机试验，共纳入514例在社区或医院接受治疗的滤泡性、巨球蛋白血症、边缘区、小淋巴细胞性或套细胞淋巴瘤患者，比较了2种方案的无进展生存期。受试者随机分组，最多接受6个周期的苯达莫司汀(90 mg/m²，第1和第2天)+利妥昔单抗(375 mg/m²，第1天)，或CHOP(环磷酰胺750 mg/m²，第1天；阿霉素50 mg/m²，第1天；长春新碱1.4 mg/m²，第1天；强的松100 mg，第1~5天)+利妥昔单抗(375 mg/m²，第1天)。两组分别纳入261例和253例患者。

结果显示，苯达莫司汀-利妥昔单抗组患者的中位无进展生存期为69.5个月，而CHOP-利妥昔单抗组仅为31.2个月。苯达莫司汀-利妥昔单抗的生存优势存在于几乎所有的组织学亚组，仅有边缘区淋巴瘤例外。

在乳酸脱氢酶水平正常的患者中(占62%)，苯达莫司汀-利妥昔单抗可显著延长无进展生存期(P＜0.001)；而在乳酸脱氢酶水平升高的患者中(占38%)，该方案虽仍可延长无进展生存期，但不具有显著性(P=0.118)。在滤泡性淋巴瘤患者中，滤泡性淋巴瘤国际预后指数(FLIPI)为0~2(良好)和3~5(不良)的2个亚组接受苯达莫司汀-利妥昔单抗治疗更有利于延长无进展生存期，P值分别为0.043和0.068。

在苯达莫司汀-利妥昔单抗组中有74例患者接受了抢救治疗，而CHOP-利妥昔单抗组为116例。在后者中，52例患者采用苯达莫司汀-利妥昔单抗作为抢救方案。两组的总生存率相似，分别发生43例和45例死亡。两组分别观察到20例和23例第二恶性肿瘤，两组各有1例血液恶性肿瘤(苯达莫司汀-利妥昔单抗组有1例骨髓增生异常综合征，CHOP-利妥昔单抗组有1例急性粒细胞性白血病)。

苯达莫司汀-利妥昔单抗组的3/4级血液毒性显著少于CHOP-利妥昔单抗组(P＜0.0001)。发生白细胞减少的治疗周期所占比例，苯达莫司汀-利妥昔单抗组为12%，CHOP-利妥昔单抗组则高达38%。发生中性粒细胞减少的治疗周期所占比例，两组分别为11%和46%。苯达莫司汀-利妥昔单抗组需要使用粒细胞集落刺激因子(G-CSF)的治疗周期所占比例也显著低于CHOP-利妥昔单抗组(4% vs. 20%)。两组的贫血和血小板减少发生率相似，均较低(仅在不到2%的治疗周期中发生)。

值得一提的是，脱发在苯达莫司汀-利妥昔单抗组患者中未出现，而在CHOP-利妥昔单抗组中相当多见。此外，两组中感觉异常的发生率分别为18/261和73/253，分别有16例和73例患者发生口炎，P值均＜0.0001.

不过，苯达莫司汀-利妥昔单抗组中红斑(42/261 vs. 23/253)和过敏反应(40例 vs. 15例)更多见。二者均不是剂量依赖性毒性。感染并发症较常见，两组分别有96例和127例患者受累。

研究者称下一步将开展名为维持的新试验，将在591例患者中评价利妥昔单抗维持治疗的效果。受试者将接受2年利妥昔单抗维持治疗，继而随机分组接受观察或再接受2年利妥昔单抗维持治疗。

Rummel博士披露称接受了由萌蒂制药和罗氏提供的酬金和研究资助。

 

CHICAGO (EGMN)–Bendamustine-rituximab continues to outshine CHOP-rituximab for indolent and mantle cell lymphomas, based on the updated results of the StiL NHL1 study.

With a twofold higher rate of progression-free survival and several-fold reductions in the rates of associated toxicities, “bendamustine-rituximab could be considered the preferred first-line treatment for patients with these disease entities,” Dr. Mathias J. Rummel said during a press conference at the annual meeting of the American Society of Clinical Oncology.

Bendamustine was developed 50 years ago in East Germany, Dr. Rummel said. Only after the reunification of Germany did physicians in the West learn about the drug and begin to conduct clinical trials and to publish the results.

A large randomized trial of 514 evaluable patients treated in community and hospital-based oncology groups in Germany, StiL NHL1 compared progression-free survival for the two regimens in patients with follicular, Waldenstrom’s, marginal zone, small lymphocytic, or mantle cell lymphomas.

Patients in the bendamustine-rituximab group had a median of 69.5 months of progression-free survival compared with 31.2 months with CHOP-rituximab. The benefit with bendamustine-rituximab was maintained in all histological subtypes except marginal zone lymphoma.

In patients with normal levels of lactic dehydrogenase (62%), progression-free survival was significantly prolonged with bendamustine-rituximab compared with CHOP-rituximab (P less than .001). In those with elevated levels of LDH (38%), progression-free survival was numerically, but not significantly, increased with bendamustine-rituximab (P = .118).

In patients with follicular lymphoma, follicular lymphoma international prognostic index (FLIPI) subgroups defined by 0-2 factors (favorable) and 3-5 factors (unfavorable) had longer progression-free survival with bendamustine-rituximab than with CHOP-rituximab. The longer progression-free survival was significant for both the favorable (P = .043) and unfavorable (P = .068) FLIPI subgroups.

Patients in the study were randomized for a maximum of six cycles to either bendamustine (90 mg/m² on day 1 and 2) and rituximab (375 mg/m² on day 1) or to CHOP-rituximab (cyclophosphamide 750 mg/m² on day 1, doxorubicin 50 mg/m² on day 1, vincristine 1.4 mg/m² on day 1, and prednisone 100 mg on days 1-5), and rituximab (375 mg/m² on day 1), according to Dr. Rummel of the University Hospital Giessen (Germany).

In the bendamustine-rituximab group, 74 salvage treatments had been initiated. In the CHOP-rituximab group, 116 salvage treatments were initiated. Of those in the CHOP-rituximab group, 52 patients received bendamustine-rituximab as a salvage regimen. Overall survival did not differ between the treatment arms, with 43 and 45 deaths in the two groups, respectively. Secondary malignancies were observed in 20 patients in the bendamustine-rituximab group compared with 23 in the CHOP-rituximab group, with 1 hematologic malignancy in each group (1 case of myelodysplastic syndrome in the bendamustine-rituximab group and 1 case of acute myelogenous leukemia in the CHOP-rituximab group).

Grade 3/4 hematotoxicities were significantly lower in the 261 patients in the bendamustine-rituximab group than in the 253 in the CHOP-rituximab group (P less than .0001). The percentage of cycles associated with leukopenia was 12% for bendamustine-rituximab patients and 38% for CHOP-rituximab patients. The percentage of cycles associated with neutropenia was nearly 11% with bendamustine-rituximab and more than 46% with CHOP-rituximab. The percentage of cycles that necessitated administration of granulocyte colony-stimulating factor (G-CSF) was 4% with bendamustine-rituximab and 20% with CHOP-rituximab. The rates of anemia and thrombocytopenia were comparable and low (less than 2% of cycles) for both regimens.

Importantly, alopecia did not occur with bendamustine-rituximab but was nearly universal with CHOP-rituximab, Dr. Rummel said. Paresthesias were noted in 18 of 261 bendamustine-rituximab patients and 73 of 253 CHOP-rituximab patients; stomatitis was seen in 16 and 73 patients, respectively. Both differences were significant (P less than .0001).

Conversely, the bendamustine-treated patients had more erythema (42 of 261 bendamustine-rituximab patients vs. 23 of 253 CHOP-rituximab patients) and allergic reactions (40 vs. 15, respectively). These were not dose-limiting toxicities. Infectious complications were frequent, and affected 96 bendamustine and 127 CHOP patients.

Next steps include a new trial called MAINTAIN that will examine rituximab maintenance therapy in 591 patients treated with bendamustine and rituximab. Patients will receive 2 years of rituximab maintenance therapy and will then be randomized to either observation or 2 more years of rituximab.

Dr. Rummel receives honoraria and research funding from Mundipharma and Roche.