Shea Lauren, Watkins Marcus P, Wan Fei, Cashen Amanda F, Wagner-Johnston Nina D, Jacoby Meagan A, Abboud Camille N, Dipersio John F, Hurd David D, Jaglowski Samantha M, Bartlett Nancy L, Fehniger Todd A
Division of Oncology, Washington University School of Medicine, St. Louis, Missouri.
Division of Biostatistics, Washington University School of Medicine, St. Louis, Missouri.
Biol Blood Marrow Transplant. 2020 Dec;26(12):2223-2228. doi: 10.1016/j.bbmt.2020.08.017. Epub 2020 Aug 20.
For patients with relapsed or refractory classical Hodgkin lymphoma (cHL), salvage chemotherapy followed by consolidation with autologous stem cell transplant (ASCT) remains the standard of care. Even with this aggressive treatment strategy, 5-year progression-free survival is ≤50%, and there remains interest in maintenance strategies to improve long-term disease-free survival. Lenalidomide is an immunomodulatory agent with demonstrated activity in multiple subtypes of lymphoma including cHL, and has also been shown to improve both progression-free and overall survival as maintenance therapy after ASCT in multiple myeloma. This multicenter study evaluated maintenance lenalidomide after ASCT for patients with cHL. Patients were enrolled 60 to 90 days post-transplant and received oral lenalidomide on days 1 to 28 of 28-day cycles for a maximum of 18 cycles. Lenalidomide was started at 15 mg daily and increased to maximum of 25 mg daily if tolerated. The primary objective of this study was to assess the feasibility of this regimen, with a goal <30% rate of discontinuation at or before cycle 12 for drug-related reasons. Twenty-seven patients were enrolled and 26 received at least 1 dose of lenalidomide. With a median follow-up of 51.3 months (range, 12.2 to 76.2 months), 23 of 26 patients were alive. Median event-free survival was 9.4 months and median progression-free survival had not been reached, with 17 of 26 patients (65.4%) remaining in remission at last follow-up. Excluding 4 patients who discontinued therapy for progression and 2 who discontinued due to noncompliance, the discontinuation rate at or before cycle 12 was 52%. Treatment was complicated by a high frequency of hematologic adverse events, with 15 patients (58%) experiencing grade 3 to 4 hematologic toxicity and 5 (19%) experiencing grade 4 hematologic toxicity. We conclude that the regimen of maintenance lenalidomide explored in this study is not feasible for patients with cHL immediately following ASCT. An alternative lenalidomide dose or schedule may be better tolerated following ASCT for patients with relapsed or refractory cHL.
对于复发或难治性经典型霍奇金淋巴瘤(cHL)患者,挽救性化疗后行自体干细胞移植(ASCT)巩固治疗仍是标准治疗方案。即便采用这种积极的治疗策略,5年无进展生存率仍≤50%,因此人们仍对改善长期无病生存的维持治疗策略感兴趣。来那度胺是一种免疫调节剂,已证明其在包括cHL在内的多种淋巴瘤亚型中具有活性,并且在多发性骨髓瘤中,来那度胺作为ASCT后的维持治疗也已显示可改善无进展生存期和总生存期。这项多中心研究评估了ASCT后给予cHL患者来那度胺维持治疗的效果。患者在移植后60至90天入组,在28天周期的第1至28天口服来那度胺,最多18个周期。来那度胺起始剂量为每日15 mg,若耐受则增至每日最大剂量25 mg。本研究的主要目的是评估该方案的可行性,目标是在第12周期或之前因药物相关原因停药率<30%。27例患者入组,26例接受了至少1剂来那度胺。中位随访51.3个月(范围12.2至76.2个月),26例患者中有23例存活。中位无事件生存期为9.4个月,中位无进展生存期尚未达到,26例患者中有17例(65.4%)在最后一次随访时仍处于缓解状态。排除4例因疾病进展停药的患者和2例因不依从停药的患者,第12周期或之前的停药率为52%。治疗因血液学不良事件发生率高而变得复杂,15例患者(58%)发生3至4级血液学毒性,5例(19%)发生4级血液学毒性。我们得出结论,本研究中探索的来那度胺维持治疗方案对ASCT后的cHL患者不可行。对于复发或难治性cHL患者,ASCT后采用其他来那度胺剂量或给药方案可能耐受性更好。