Padrnos Leslie, Ernst Brenda, Dueck Amylou C, Kosiorek Heidi E, Ginos Brenda F, Toro Angela, Johnston Patrick B, Habermann Thomas M, Leis Jose F, Mikhael Joseph R, Nowakowski Grzegorz S, Colgan Joseph, Porrata Luis, Ansell Stephen M, Witzig Thomas E, Reeder Craig
Department of Hematology Oncology, Mayo Clinic Arizona, Phoenix, AZ.
Department of Hematology Oncology, Mayo Clinic Jacksonville, Jacksonville, FL.
Clin Lymphoma Myeloma Leuk. 2018 Oct;18(10):664-672.e2. doi: 10.1016/j.clml.2018.06.013. Epub 2018 Jun 15.
Treatment outcomes have improved in lymphoid malignancies but relapse remains inevitable for most patients. Everolimus and lenalidomide have shown clinical activity as single agents in patients with relapsed and refractory Hodgkin and non-Hodgkin lymphomas.
The present phase I/II trial for patients with relapsed and refractory lymphoid malignancy opened at Mayo Clinic from January 2011 to May 2013. The trial used a standard cohort 3 + 3 design to determine the maximum tolerated dose for the combination. Stem cell transplantation had failed in 27 of the patients (49%), 63% had stage IV disease, and ≥ 3 previous therapies had failed in 78%.
Of the 58 patients, enrolled, 55 were evaluable for analysis. The maximum tolerated dose was 5 mg/d for everolimus plus 10 mg/d for 21 days for lenalidomide. The most common grade ≥ 3 toxicities were hematologic and included neutropenia (56%), leukopenia (38%), and thrombocytopenia (33%). Seven patients discontinued the study because of adverse events. One patient died of disease progression. The overall response rate was 27% (15 of 55), with 38% (21 of 55) having stable disease.
The present phase I/II trial of everolimus and lenalidomide for R/R lymphoma has shown the combination to be tolerable, with neutropenia as the main dose-limiting toxicity. Encouraging responses were seen in this heavily pretreated group, and the patients with a response had meaningful duration of response.
淋巴系统恶性肿瘤的治疗效果已有改善，但对大多数患者而言，复发仍难以避免。依维莫司和来那度胺作为单一药物，在复发难治性霍奇金淋巴瘤和非霍奇金淋巴瘤患者中已显示出临床活性。
本针对复发难治性淋巴系统恶性肿瘤患者的I/II期试验于2011年1月至2013年5月在梅奥诊所开展。该试验采用标准的3 + 3队列设计来确定联合用药的最大耐受剂量。27例患者（49%）干细胞移植失败，63%患者为IV期疾病，78%患者既往≥3线治疗失败。
入组的58例患者中，55例可进行疗效评估。依维莫司的最大耐受剂量为5 mg/d，来那度胺为10 mg/d，连用21天。最常见的≥3级毒性为血液学毒性，包括中性粒细胞减少（56%）、白细胞减少（38%）和血小板减少（33%）。7例患者因不良事件中止研究。1例患者死于疾病进展。总缓解率为27%（55例中的15例），疾病稳定率为38%（55例中的21例）。
本次依维莫司和来那度胺用于复发/难治性淋巴瘤的I/II期试验表明，该联合用药耐受性良好，中性粒细胞减少是主要的剂量限制性毒性。在这个经过大量预处理的患者群体中观察到了令人鼓舞的反应，且有反应的患者缓解期有意义。
