Rituximab dose-escalation trial in chronic lymphocytic leukemia
Rituximab dose-escalation trial in chronic lymphocytic leukemia
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DOI：
10.1200/jco.2001.19.8.2165
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发表时间：
2001-04-15
影响因子：
45.3
通讯作者：
Keating, MJ
中科院分区：
文献类型：
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作者：
O'Brien, SM;Kantarjian, H;Keating, MJ
目的：在慢性淋巴细胞白血病（CLL）患者中进行利妥昔单抗剂量递增试验，以确定最大耐受剂量（MTD），评估高循环淋巴细胞计数患者的首次给药反应，并评估较高与较低剂量的疗效。50名CLL（n = 40）或其它成熟B细胞淋巴样白血病（n = 10）患者每周输注4次利妥昔单抗。所有患者的首次剂量为375 mg/m2;剂量递增从第2次剂量开始，但每个患者的剂量保持不变。结果：首次给药（375 mg/m2）时，94%的患者出现毒性反应，但大多数患者的毒性反应为1 ~ 2级，主要为发热和寒战。6名患者（12%）在首次给药时出现严重毒性，包括所有6名患者的发热、寒战、呼吸困难和缺氧，5名患者的低血压和1名患者的高血压。在达到2，250 mg/m2的剂量之前，后续剂量的毒性最小。12例患者中有8例（67%）出现2级毒性，包括发热、寒战、恶心和不适，但无患者出现3级或4级毒性。首次给药的严重毒性在其他B细胞白血病患者中明显更常见，10例患者中有5例（50%）发生，而40例CLL患者中有1例（2%）发生（P <0.001）。总体缓解率为40%; CLL患者的所有缓解均为部分缓解。CLL的缓解率为36%，其他B细胞淋巴样白血病的缓解率为60%。反应与剂量相关：500至825 mg/m2治疗的患者为22%，1，000 mg/m2治疗的患者为43%，最高剂量2，250 mg/m2治疗的患者为75%（P = 0.007）。至疾病进展的中位时间为8个月。结论：利妥昔单抗在高剂量水平下对慢性淋巴细胞白血病患者有显著的疗效。严重的首次给药反应在CLL患者中并不常见，即使循环淋巴细胞计数较高，但在CD 20表面表达增加的其他成熟B细胞白血病患者中较为常见。利妥昔单抗的疗效在这组患者中也很显著。 2001年，美国临床肿瘤学会。
Purpose: To conduct a dose-escalation trial of rituximab in patients with chronic lymphocytic leukemia (CLL) to define the maximum-tolerated dose (MTD), to evaluate first-dose reactions in patients with high circulating lymphocyte counts, and to assess the efficacy at higher versus lower doses.Patients and Methods: fifty patients with CLL (n = 40) or other mature B-cell lymphoid leukemias (n = 10) were treated with four weekly infusions of rituximab. The first dose was 375 mg/m(2) for ail patients; dose-escalation began with dose 2 but was held constant for each patient. Escalated doses were from 500 to 2,250 mg/m(2).Results: Toxicity with the first dose (375 mg/m(2)) was noted in 94% of patients hut was grade 1 or 2 in most, predominantly fever and chills. Six patients (12%) experienced severe toxicity with the first dose, including fever, chills, dyspnea, and hypoxia in all six patients, hypotension in five, and hypertension in one. Toxicity on subsequent doses was minimal until a dose of 2,250 mg/m(2) was achieved. Eight (67%) of 12 patients had grade 2 toxicity, including fever, chills, nausea, and malaise, although no patient had grade 3 or 4 toxicity. Severe toxicity with the first dose was significantly more common in patients with other B-cell leukemias, occurring in five (50%) of 10 patients versus one (2%) of 40 patients with CLL (P < .001). The overall response rate was 40%; all responses in patients with CLL were partial remissions. Response rates were 36% in CLL and 60% in other B-cell lymphoid leukemias. Response was correlated with dose: 22% for patients treated at 500 to 825 mg/m(2), 43% for those treated at 1,000 ta 1,500 mg/m(2), and 75% for those treated at the highest dose of 2,250 mg/m(2) (P = .007). The median time to disease progression was 8 months. Myelosuppression and infections were uncommon.Conclusion: Rituximab has significant activity in patients with CLL at the higher dose levels. Severe first-dose reactions were uncommon in patients with CLL, even with high circulating lymphocyte counts, but were frequent in patients with other mature B-cell leukemias in which CD20 surface expression is increased. Efficacy of rituximab was also significant in this group of patients. 2001 by American Society of Clinical Oncology.