Division of Hematology, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio.
College of Pharmacy, The Ohio State University, Columbus, Ohio.
Clin Cancer Res. 2020 Dec 1;26(23):6187-6195. doi: 10.1158/1078-0432.CCR-20-1280. Epub 2020 Sep 21.
Infectious complications constitute a leading cause of morbidity and mortality in chronic lymphocytic leukemia (CLL). Patients respond poorly to vaccines, particularly pneumococcal polysaccharide and influenza vaccines. In addition, patients with genetically high-risk disease are at increased risk for early disease progression and death. Lenalidomide, an oral immunomodulatory agent with demonstrated clinical activity in CLL, can potentially restore immune system dysfunction associated with CLL while improving disease outcomes.
Phase II study randomized 49 patients with genetically high-risk CLL or small lymphocytic lymphoma [SLL; defined as unmutated Ig heavy chain variable region, deletion(17p) or (11q), and/or complex abnormal karyotype], to receive lenalidomide either concurrent (arm A) or sequential to (arm B) two doses of 13-valent protein-conjugated pneumococcal vaccine (PCV13) administered 2 months apart, in patients not meeting International Workshop on Chronic Lymphocytic Leukemia treatment criteria.
Four serotypes (3, 4, 5, 6B) achieved the additional seroprotection definition of a fourfold increase in arm A, and six serotypes (3, 4, 5, 6B, 19A, 19F) in arm B. All patients achieved the defined concentration of 0.35 μg/mL for at least one serotype tested. No significant difference was observed with the addition of lenalidomide. At median time on treatment of 3.6 years, median progression-free survival (PFS) was 5.8 years [95% confidence interval (CI), 3.1-not reached]. PFS at 1, 2, and 3 years was 85% (95% CI, 72-93), 79% (95% CI, 64-88), and 72% (95% CI, 57-83), respectively.
Lenalidomide is efficacious with manageable toxicities as an early intervention strategy in patients with high-risk CLL, but did not enhance humoral response to PCV13 vaccine.
感染并发症是慢性淋巴细胞白血病（CLL）发病率和死亡率的主要原因。患者对疫苗的反应不佳，尤其是肺炎球菌多糖疫苗和流感疫苗。此外，遗传高危疾病患者发生早期疾病进展和死亡的风险增加。来那度胺是一种口服免疫调节药物，在 CLL 中具有临床活性，可潜在恢复与 CLL 相关的免疫系统功能障碍，同时改善疾病结局。
这项 II 期研究将 49 例遗传高危 CLL 或小淋巴细胞淋巴瘤[SLL；定义为未突变的 Ig 重链可变区、缺失（17p）或（11q）和/或复杂异常核型]患者随机分为两组：一组接受来那度胺联合（A 组）或序贯（B 组）治疗，即在接受两剂相隔 2 个月的 13 价蛋白结合肺炎球菌疫苗（PCV13）后，在不符合国际慢性淋巴细胞白血病工作组治疗标准的情况下接受来那度胺治疗；两组患者均未接受治疗。
A 组 4 种血清型（3、4、5、6B）达到了血清型保护定义的 4 倍增加，B 组 6 种血清型（3、4、5、6B、19A、19F）达到了血清型保护定义的 4 倍增加。所有患者至少有一种检测血清型的浓度达到 0.35 μg/ml。来那度胺的添加没有观察到显著差异。中位治疗时间为 3.6 年，中位无进展生存期（PFS）为 5.8 年[95%置信区间（CI），3.1-未达到]。1、2、3 年时的 PFS 分别为 85%（95%CI，72%-93%）、79%（95%CI，64%-88%）和 72%（95%CI，57%-83%）。
来那度胺作为高危 CLL 患者的早期干预策略，疗效确切且毒性可耐受，但并未增强对 PCV13 疫苗的体液反应。
