Bing Center for Waldenström Macroglobulinemia, Dana-Farber Cancer Institute, Boston, MA.
Department of Medicine, Harvard Medical School, Boston, MA.
Blood Adv. 2022 Feb 8;6(3):1015-1024. doi: 10.1182/bloodadvances.2021006106.
Bruton tyrosine kinase (BTK) inhibitors are the only FDA-approved treatments for Waldenström macroglobulinemia (WM). Factors prognostic of survival and predictive of response to BTK inhibitors remained to be clarified. We evaluated 319 patients with WM to identify predictive and prognostic factors on ibrutinib monotherapy. Logistic and Cox proportional-hazard regression models were fitted for response and survival. Multiple imputation analyses were used to address bias associated with missing data. Major (partial response or better) and deep responses (very good partial response or better) were attained in 78% and 28% of patients. CXCR4 mutations were associated with lower odds of major (odds ratio [OR], 0.2; 95% confidence interval [CI], 0.1-0.5; P < .001) and deep response (OR, 0.3; 95% CI, 0.2-0.6; P = .001). CXCR4 mutations (hazard ratio [HR], 2.0; 95% CI, 1.2-3.4; P = .01) and platelet count 100 K/uL or less (HR, 2.5; 95% CI, 1.3-4.9; P = .007) were associated with worse progression-free survival (PFS). We proposed a scoring system using these 2 factors. The median PFS for patients with 0, 1, and 2 risk factors were not reached, 5 years and 3 years (P < .001). Patients with 2 risk factors had HR 2.2 (95% CI, 1.3-3.8; P = .004) compared with 1 factor, and patients with 1 factor had HR 2.3 (95% CI, 1.1-5.1; P = .03) compared with 0 factors. Age ≥65 years was the only factor associated with overall survival (HR, 3.2; 95% CI, 1.4-7.0; P = .005). Multiple imputation analyses did not alter our results. Our study confirms the predictive and prognostic value of CXCR4 mutations in patients with WM treated with ibrutinib monotherapy.
布鲁顿酪氨酸激酶 (BTK) 抑制剂是唯一获得美国食品药品监督管理局批准用于治疗华氏巨球蛋白血症 (WM) 的药物。生存的预后因素和对 BTK 抑制剂反应的预测因素仍有待阐明。我们评估了 319 例 WM 患者，以确定伊布替尼单药治疗的预测和预后因素。逻辑回归和 Cox 比例风险回归模型用于反应和生存分析。采用多重插补分析处理缺失数据相关的偏倚。78%的患者达到主要（部分缓解或更好）和深度缓解（非常好的部分缓解或更好）。CXCR4 突变与主要缓解（优势比 [OR]，0.2；95%置信区间 [CI]，0.1-0.5；P <.001）和深度缓解（OR，0.3；95%CI，0.2-0.6；P =.001）的可能性降低相关。CXCR4 突变（风险比 [HR]，2.0；95%CI，1.2-3.4；P =.01）和血小板计数 100 K/uL 或更低（HR，2.5；95%CI，1.3-4.9；P =.007）与无进展生存期（PFS）较差相关。我们提出了一个使用这两个因素的评分系统。无风险因素、1 个风险因素和 2 个风险因素的患者的中位 PFS 分别未达到、5 年和 3 年（P <.001）。与 1 个因素相比，有 2 个风险因素的患者 HR 为 2.2（95%CI，1.3-3.8；P =.004），而有 1 个因素的患者 HR 为 2.3（95%CI，1.1-5.1；P =.03）与 0 个因素相比。年龄≥65 岁是唯一与总生存期相关的因素（HR，3.2；95%CI，1.4-7.0；P =.005）。多重插补分析并未改变我们的结果。我们的研究证实了 CXCR4 突变在接受伊布替尼单药治疗的 WM 患者中的预测和预后价值。
