Denileukin diftitox in combination with rituximab for previously untreated follicular B-cell non-Hodgkin's lymphoma.
Denileukin diftitox in combination with rituximab for previously untreated follicular B-cell non-Hodgkin's lymphoma.
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滤泡性淋巴瘤表现为瘤内浸润的非恶性T淋巴细胞，包括CD 4 + CD 25+调节性T（Treg）细胞。我们在先前未经治疗的晚期滤泡性淋巴瘤患者中将地尼白介素diftitox与利妥昔单抗组合，预期地尼白介素diftitox将耗尽CD 25 + Treg细胞，而利妥昔单抗将耗尽恶性B细胞。患者接受利妥昔单抗375 mg/m2每周一次，持续4周，地尼白介素18 mcg/kg/天，每3周一次，持续5天，持续4个周期;两种药物均不作为维持治疗。2008年8月至2010年3月期间，入组了24例患者。1例患者在治疗前死亡，未纳入分析。23例患者中有11例（48%; 95% CI：27-69%）缓解; 2例（9%）完全缓解，9例（39%）部分缓解。2年时无进展率为55%（95%CI：37-82%）。13例患者（57%）发生≥3级不良事件，1例患者（4%）死亡。在相关研究中，治疗后可溶性CD 25和CD 25 + T细胞数量下降，但IL-15和IP-10代偿性增加。我们得出的结论是，虽然在利妥昔单抗中添加地尼白细胞毒素减少了CD 25 + T细胞的数量，但地尼白细胞毒素增加了该组合的毒性，而没有改善缓解率或进展时间。
Follicular lymphoma exhibits intratumoral infiltration by non-malignant T lymphocytes inluding CD4+CD25+ regulatory T (Treg) cells. We combined denileukin diftitox with rituximab in previously untreated, advanced-stage follicular lymphoma patients anticipating that denileukin diftitox would deplete CD25+ Treg cells while rituximab would deplete malignant B-cells. Patients received rituximab 375 mg/m2 weekly for 4 weeks and denileukin diftitox 18 mcg/kg/day for 5 days every 3 weeks for 4 cycles; neither agent was given as maintenance therapy. Between August 2008 and March 2010, 24 patients were enrolled. One patient died before treatment was given and was not included in the analysis. Eleven of 23 patients (48%; 95% CI: 27–69%) responded; 2 (9%) had complete responses and 9 (39%) had partial responses. The progression-free rate at 2 years was 55% (95%CI: 37–82%). Thirteen patients (57%) experienced grade ≥3 adverse events and 1 patient (4%) died. In correlative studies, soluble CD25 and the number of CD25+ T-cells decreased after treatment, however there was a compensatory increase in IL-15 and IP-10. We conclude that while the addition of denileukin diftitox to rituximab decreased the number of CD25+ T-cells, denileukin diftitox contributed to the toxicity of the combination without an improvement in response rate or time to progression.
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影响因子：
20.3
作者：
Yang, Zhi-Zhang;Novak, Anne J.;Ansell, Stephen M.
通讯作者：
Ansell, Stephen M.
影响因子：
4.4
作者：
Liyanage, UK;Moore, TT;Linehan, DC
通讯作者：
Linehan, DC
影响因子：
11.2
作者：
Yang ZZ;Novak AJ;Ziesmer SC;Witzig TE;Ansell SM
通讯作者：
Ansell SM
影响因子：
3.7
作者：
KAPLAN, EL;MEIER, P
通讯作者：
MEIER, P
DOI：
10.4049/jimmunol.181.5.3285
发表时间：
2008-09-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Vang KB;Yang J;Mahmud SA;Burchill MA;Vegoe AL;Farrar MA
通讯作者：
Farrar MA