Medical Oncology Service.
Laboratory of Molecular Biology.
Blood Adv. 2021 Dec 14;5(23):4807-4816. doi: 10.1182/bloodadvances.2021005039.
Hairy cell leukemia variant (HCLv) responds poorly to purine analogue monotherapy. Rituximab concurrent with cladribine (CDAR) improves response rates, but long-term outcomes are unknown. We report final results of a phase 2 study of CDAR for patients with HCLv. Twenty patients with 0 to 1 prior courses of cladribine and/or rituximab, including 8 who were previously untreated, received cladribine 0.15 mg/kg on days 1 to 5 with 8 weekly rituximab doses of 375 mg/m2 beginning day 1. Patients received a second rituximab course ≥6 months after cladribine, if and when minimal residual disease (MRD) was detected in blood. The complete remission (CR) rate from CDAR was 95% (95% confidence interval, 75-100). Sixteen (80%) of 20 patients (95% confidence interval, 56-94) became MRD negative according to bone marrow at 6 months. The median duration of MRD-negative CR was 70.1 months, and 7 of 16 are still MRD negative up to 120 months. With a median follow-up of 69.7 months, 11 patients received delayed rituximab, and the 5-year progression-free survival (PFS) and overall survival (OS) were 63.3% and 73.9%, respectively. Five patients with TP53 mutations had shorter PFS (median, 36.4 months vs unreached; P = .0024) and OS (median, 52.4 months vs unreached; P = .032). MRD-negative CR at 6 months was significantly associated with longer PFS (unreached vs 17.4 months; P < .0001) and OS (unreached vs 38.2 months; P < .0001). Lack of MRD in blood at 6 months was also predictive of longer PFS and OS (P < .0001). After progression following CDAR, median OS was 29.7 months. CDAR is effective in HCLv, with better outcomes in patients who achieve MRD-negative CR. This trial is registered at www.clinicaltrials.gov as #NCT00923013.
毛细胞白血病变异型（HCLv）对嘌呤类似物单药治疗反应不佳。利妥昔单抗联合克拉屈滨（CDAR）可提高缓解率，但长期结果尚不清楚。我们报告了 HCLv 患者接受 CDAR 治疗的 2 期研究的最终结果。20 例患者（0 至 1 次接受克拉屈滨和/或利妥昔单抗治疗，包括 8 例初治患者）接受克拉屈滨 0.15mg/kg，每日 1 次至 5 次，同时在第 1 天给予 8 周 1 次 375mg/m2 的利妥昔单抗。如果在血液中检测到微小残留病（MRD），则在克拉屈滨后≥6 个月接受第二剂利妥昔单抗。CDAR 的完全缓解（CR）率为 95%（95%置信区间，75-100）。20 例患者中有 16 例（80%，95%置信区间，56-94）在 6 个月时骨髓符合 MRD 阴性。MRD 阴性 CR 的中位持续时间为 70.1 个月，16 例中有 7 例至 120 个月仍为 MRD 阴性。中位随访 69.7 个月后，11 例患者接受了延迟利妥昔单抗治疗，5 年无进展生存（PFS）和总生存（OS）分别为 63.3%和 73.9%。5 例携带 TP53 突变的患者 PFS 更短（中位，36.4 个月 vs 未达到；P =.0024）和 OS 更短（中位，52.4 个月 vs 未达到；P =.032）。6 个月时 MRD 阴性 CR 与更长的 PFS（未达到 vs 17.4 个月；P <.0001）和 OS（未达到 vs 38.2 个月；P <.0001）显著相关。6 个月时血液中无 MRD 也预测了更长的 PFS 和 OS（P <.0001）。在 CDAR 后进展后，中位 OS 为 29.7 个月。CDAR 对 HCLv 有效，MRD 阴性 CR 患者的结局更好。该试验在 www.clinicaltrials.gov 上注册为#NCT00923013。
