Phase I/II trial of everolimus in combination with bortezomib and rituximab (RVR) in relapsed/refractory Waldenstrom macroglobulinemia.
Phase I/II trial of everolimus in combination with bortezomib and rituximab (RVR) in relapsed/refractory Waldenstrom macroglobulinemia.
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依维莫司联合硼替佐米和利妥昔单抗 (RVR) 治疗复发/难治性华氏巨球蛋白血症的 I/II 期试验。
作者：
Ghobrial,IM;Redd,R;Armand,P;Banwait,R;Boswell,E;Chuma,S;Huynh,D;Sacco,A;Roccaro,AM;Perilla-Glen,A;Noonan,K;MacNabb,M;Leblebjian,H;Warren,D;Henrick,P;Castillo,JJ;Richardson,PG;Matous,J;Weller,E;Treon,SP
我们在I/II期研究中检查了雷帕霉素抑制剂依维莫司与硼替佐米和利妥昔单抗在复发性/难治性Waldenstrom巨球蛋白血症（WM）患者中的组合。所有患者均接受6个周期的依维莫司/利妥昔单抗或依维莫司/硼替佐米/利妥昔单抗联合治疗，随后用依维莫司维持治疗直至进展。46例患者接受了治疗; 98%的患者既往接受过利妥昔单抗，57%的患者既往接受过硼替佐米。在I期试验中未观察到剂量限制性毒性。最常见的所有等级的治疗相关毒性为疲乏（63%）、贫血（54%）、白细胞减少（52%）、中性粒细胞减少（48%）和腹泻（43%）。46例患者中有36例（78%）接受了三种药物的全剂量治疗（FDT）。在这36例患者中，2例（6%）完全缓解（90%置信区间（CI）：1-16）。总体而言，32/36例（89%）患者至少出现了轻微缓解（90% CI：76-96%）。观察到的部分缓解或更好缓解率为19/36（53，90 CI：38-67%）。对于36例FDT患者，中位无进展生存期为21个月（95% CI：12-无法估计）。总之，这项研究表明，依维莫司，硼替佐米和利妥昔单抗的组合是耐受性良好，即使在先前治疗的患者中也达到了89%的应答率，使其成为WM中基于非化疗的组合治疗的可能模型。
We examined the combination of the mammalian target of rapamycin inhibitor everolimus with bortezomib and rituximab in patients with relapsed/refractory Waldenstrom macroglobulinemia (WM) in a phase I/II study. All patients received six cycles of the combination of everolimus/rituximab or everolimus/bortezomib/rituximab followed by maintenance with everolimus until progression. Forty-six patients were treated; 98% received prior rituximab and 57% received prior bortezomib. No dose-limiting toxicities were observed in the phase I. The most common treatment-related toxicities of all grades were fatigue (63%), anemia (54%), leucopenia (52%), neutropenia (48%) and diarrhea (43%). Thirty-six (78%) of the 46 patients received full dose therapy (FDT) of the three drugs. Of these 36, 2 (6%) had complete response (90% confidence interval (CI): 1–16). In all, 32/36 (89%) of patients experienced at least a minimal response (90% CI: 76–96%). The observed partial response or better response rate was 19/36 (53, 90 CI: 38–67%). For the 36 FDT patients, the median progression-free survival was 21 months (95% CI: 12–not estimable). In summary, this study demonstrates that the combination of everolimus, bortezomib and rituximab is well tolerated and achieved 89% response rate even in patients previously treated, making it a possible model of non-chemotherapeutic-based combination therapy in WM.