Front-line, dose-escalated immunochemotherapy is associated with a significant progression-free survival advantage in patients with double-hit lymphomas: a systematic review and meta-analysis
Front-line, dose-escalated immunochemotherapy is associated with a significant progression-free survival advantage in patients with double-hit lymphomas: a systematic review and meta-analysis
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DOI：
10.1111/bjh.13463
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发表时间：
2015-08-01
影响因子：
6.5
通讯作者：
Mato, Anthony
中科院分区：
文献类型：
--
作者：
Howlett, Christina;Snedecor, Sonya J.;Mato, Anthony
双重打击淋巴瘤（DHL），定义为同时MYC和BCL 2（或BCL 6）重排，与标准风险的弥漫性大B细胞淋巴瘤（DLBCL）相比，结局非常差。因此，剂量强化（DI）治疗和/或高剂量治疗和移植的巩固已在DHL中进行了探索，尽管益处一直存在争议。这项荟萃分析比较了接受剂量递增方案的DHL患者的生存结局[DI：R-Hyper-CVAD（利妥昔单抗、环磷酰胺、长春新碱、阿霉素、地塞米松）或R-CODOX-M/IVAC（利妥昔单抗、环磷酰胺、多柔比星、长春新碱、甲氨蝶呤/异环磷酰胺、依托泊苷、高剂量阿糖胞苷）;或中剂量：R-EPOCH（利妥昔单抗、依托泊苷、多柔比星、环磷酰胺、长春新碱、泼尼松）]与标准剂量方案（R-CHOP;利妥昔单抗、环磷酰胺、多柔比星、长春新碱、泼尼松）在一线治疗中的比较。在贝叶斯荟萃分析框架内使用Weibull比例风险模型对数据进行合成，以估计剂量递增治疗与R-CHOP的风险比。纳入了11项研究，检查了394例患者。患者接受一线R-CHOP（n=180）、R-EPOCH（n=91）或R-Hyper-CVAD/利妥昔单抗、甲氨蝶呤、阿糖胞苷（R-M/C）、R-CODOX-M/R-IVAC（DI）（n=123）治疗。我们的荟萃分析显示，R-CHOP、R-EPOCH和DI组的中位无进展生存期（n=350）分别为121、222和189个月。与R-CHOP相比，R-EPOCH一线治疗显著降低了疾病进展的风险（相对风险降低34%; P= 0.032）;然而，总生存期（n=374）在不同治疗方法之间无显著差异。一部分患者可能受益于有/无移植的强化诱导。有必要进一步研究移植和新型治疗组合的作用。
Double-hit lymphomas' (DHL), defined by concurrent MYC and BCL2 (or, alternatively, BCL6) rearrangements, have a very poor outcome compared to standard-risk, diffuse large B-cell lymphomas (DLBCL). Consequently, dose-intensive (DI) therapies and/or consolidation with high-dose therapy and transplant have been explored in DHL, although benefit has been debated. This meta-analysis compared survival outcomes in DHL patients receiving dose-escalated regimens [DI: R-Hyper-CVAD (rituximab, cyclophosphamide, vincristine, doxorubicin, dexamethasone) or R-CODOX-M/IVAC (rituximab, cyclophosphamide, doxorubicin, vincristine, methotrexate/ifosfamide, etoposide, high dose cytarabine); or intermediate-dose: R-EPOCH (rituximab, etoposide, doxorubicin, cyclophosphamide, vincristine, prednisone)] versus standard-dose regimens (R-CHOP; rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) in the first-line setting. Data were synthesized to estimate hazard ratios of dose-escalated treatments versus R-CHOP using a Weibull proportional hazards model within a Bayesian meta-analysis framework. Eleven studies examining 394 patients were included. Patients were treated with either front-line R-CHOP (n=180), R-EPOCH (n=91), or R-Hyper-CVAD/rituximab, methotrexate, cytarabine (R-M/C), R-CODOX-M/R-IVAC (DI) (n=123). Our meta-analysis revealed that median progression-free survival (n=350) for the R-CHOP, R-EPOCH and DI groups was 121, 222, and 189months, respectively. First-line treatment with R-EPOCH significantly reduced the risk of a progression compared with R-CHOP (relative risk reduction of 34%; P=0032); however, overall survival (n=374) was not significantly different across treatment approaches. A subset of patients might benefit from intensive induction with/without transplant. Further investigation into the role of transplant and novel therapy combinations is necessary.