Department of Medicine, Alpert Medical School of Brown University, Providence, RI, USA.
Division of Hematology-Oncology, Rhode Island Hospital, Providence, RI, USA.
Oncologist. 2022 Jul 5;27(7):532-e542. doi: 10.1093/oncolo/oyab079.
We conducted an investigator-initiated, phase I trial of vincristine sulfate liposomal injection (VSLI) in combination with bendamustine and rituximab (BR) for indolent B-cell (BCL) or mantle cell lymphoma.
Participants received 6 cycles of standard BR with VSLI at patient-specific dose determined by the Escalation with Overdose Control (EWOC) model targeting 33% probability of dose-limiting toxicity (DLT). Maximum tolerated dose (MTD) was the primary endpoint; secondary endpoints included rates of adverse events (AEs), overall response rate (ORR), and complete response (CR). Vincristine sulfate liposomal injection is FDA approved for the treatment of patients with recurrent Philadelphia chromosome-negative (Ph-) acute lymphoblastic leukemia (ALL).
Among 10 enrolled patients, VSLI was escalated from 1.80 to 2.24 mg/m2, with one DLT (ileus) at 2.04 mg/m2. Two patients discontinued VSLI early. The most common AE included lymphopenia (100%), constipation, nausea, infusion reaction (each 60%), neutropenia, and peripheral neuropathy (50%). Grade 3/4 AE included lymphopenia (90%), neutropenia (20%), and ileus (10%), with prolonged grade ≥2 lymphopenia observed in most patients. Calculated MTD for VSLI was 2.25 mg/m2 (95% Bayesian credible interval: 2.00-2.40). Overall response was 100% with 50% CR. With median follow-up 26 months, 4/10 patients experienced recurrence and 1 died.
Vincristine sulfate liposomal injection at 2.25 mg/m2 can be safely combined with BR for indolent B-cell lymphoma, but given observed toxicities and recurrences, we did not pursue an expanded cohort.Clinical Trials Registration Number: ClinicalTrials.gov identifier NCT02257242.
我们进行了一项由研究者发起的、硫酸长春新碱脂质体注射液（VSLI）联合苯达莫司汀和利妥昔单抗（BR）治疗惰性 B 细胞（BCL）或套细胞淋巴瘤的 I 期试验。
参与者接受了 6 个周期的标准 BR 治疗，VSLI 的剂量根据通过递增与过量控制（EWOC）模型确定的患者特异性剂量进行给药，该模型的目标是 33%的剂量限制毒性（DLT）概率。最大耐受剂量（MTD）是主要终点；次要终点包括不良事件（AE）发生率、总缓解率（ORR）和完全缓解（CR）。硫酸长春新碱脂质体注射液已获得 FDA 批准用于治疗复发性费城染色体阴性（Ph-）急性淋巴细胞白血病（ALL）患者。
在 10 名入组患者中，VSLI 从 1.80 增加到 2.24mg/m2，在 2.04mg/m2 时发生了 1 例 DLT（肠梗阻）。有 2 名患者提前停用了 VSLI。最常见的 AE 包括淋巴细胞减少（100%）、便秘、恶心、输注反应（各 60%）、中性粒细胞减少和周围神经病（各 50%）。3/4 级 AE 包括淋巴细胞减少（90%）、中性粒细胞减少（20%）和肠梗阻（10%），大多数患者观察到延长的 2 级以上淋巴细胞减少。计算得出 VSLI 的 MTD 为 2.25mg/m2（95%贝叶斯可信区间：2.00-2.40）。总缓解率为 100%，CR 为 50%。中位随访 26 个月时，10 例患者中有 4 例复发，1 例死亡。
硫酸长春新碱脂质体注射液 2.25mg/m2 与 BR 联合治疗惰性 B 细胞淋巴瘤是安全的，但鉴于观察到的毒性和复发情况，我们没有进行扩大队列研究。临床试验注册号：ClinicalTrials.gov 标识符 NCT02257242。
