Vidal Liat, Gurion Ronit, Ram Ron, Raanani Pia, Bairey Osnat, Robak Tadeusz, Gafter-Gvili Anat, Shpilberg Ofer
a Davidoff Center, Rabin Medical Center , Institute of Hematology, Beilinson Hospital , Petah Tikva , Israel ;
b Sackler Faculty of Medicine , Tel Aviv University , Tel Aviv , Israel ;
Leuk Lymphoma. 2016 Sep;57(9):2047-57. doi: 10.3109/10428194.2016.1154956. Epub 2016 Mar 16.
Randomized clinical trials that compared chlorambucil to different regimens, for patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) do not support an overall survival (OS) benefit. To assess the efficacy and safety of chlorambucil as frontline treatment, we conducted a systematic review and meta-analysis of randomized controlled trials. OS was the primary outcome. Meta-analysis of 18 trials that compared purine analogs, alkylators, alemtuzumab and ibrutinib to chlorambucil demonstrated no OS benefit for therapy without chlorambucil over chlorambucil (pooled HR 0.99, 95% CI 0.91-1.08; 4133 patients). PFS was longer with purine analogs compared with chlorambucil with an increased risk of infection. The risk of secondary malignancies was not increased with chlorambucil. In conclusion, our study showed that chlorambucil is an acceptable chemotherapy backbone for unfit patients with CLL. Purine analogs should be preferred in fit younger patients because of longer PFS. Future trials should focus on unfit patients who are underrepresented in clinical trials.
比较苯丁酸氮芥与不同治疗方案用于慢性淋巴细胞白血病/小淋巴细胞淋巴瘤（CLL/SLL）患者的随机临床试验并不支持其对总生存期（OS）有获益。为评估苯丁酸氮芥作为一线治疗的疗效和安全性，我们对随机对照试验进行了系统评价和荟萃分析。OS是主要结局。对18项比较嘌呤类似物、烷化剂、阿仑单抗和依鲁替尼与苯丁酸氮芥的试验进行荟萃分析表明，不含苯丁酸氮芥的治疗方案在OS方面并不优于苯丁酸氮芥（合并风险比0.99，95%可信区间0.91 - 1.08；4133例患者）。与苯丁酸氮芥相比，嘌呤类似物的无进展生存期（PFS）更长，但感染风险增加。苯丁酸氮芥不会增加继发性恶性肿瘤的风险。总之，我们的研究表明，苯丁酸氮芥是不适合的CLL患者可接受的化疗基础用药。由于PFS更长，适合的年轻患者应首选嘌呤类似物。未来的试验应关注在临床试验中代表性不足的不适合患者。
