Lenalidomide In Combination With R-ESHAP (LR-ESHAP) In Patients With Relapsed Or Refractory Diffuse Large B-Cell Lymphoma Candidates To Autologous Stem-Cell Transplantation: A Phase 1b Study From Spanish Group Geltamo

Abstract Background Diffuse large B-cell lymphoma (DLBCL) patients with relapsed or refractory disease after rituximab-containing first-line therapy have a poor outcome with the current salvage regimens. Consequently, new drugs designed to increase the response rate of salvage regimens should be explored (Gisselbrecht et al, J Clin Oncol 2010, 28: 4184-90). We conducted a phase Ib trial (3+3 design) to establish the safety, tolerability and determination of the maximum-tolerated dose (MTD) of lenalidomide in combination with R-ESHAP (LR-ESHAP) in patients with relapsed or refractory DLBCL. Efficacy data were also collected as secondary objective. Patients and Methods Eligible patients must be refractory to, or have relapsed following, first-line treatment with rituximab in combination with an anthracycline-containing regimen, and be eligible for autologous stem-cell transplantation (ASCT). Subjects received three cycles of lenalidomide (5, 10 or 15 mg) given on days 1 to 14 of every 21-day cycle, in combination with R-ESHAP salvage chemotherapy at standard doses (rituximab 375 mg/m2 day 1, etoposide 40 mg/m2 days 1-4, cisplatine 25 mg/m2 days 1-4; citarabine 2000 mg/m2 day 5, and methilprednisolone 500 mg days 1-5). Responding patients received BEAM followed by ASCT. Results During the escalating phase, 3 patients had dose-limiting toxicity in the 15 mg cohort: 1 grade 3 angioedema, and 2 mobilization failures. The MTD was therefore established at 10 mg of lenalidomide and this cohort was expanded to further explore the safety and efficacy of LR-ESHAP. A total of 20 patients (3, 13, and 4 in the 5, 10, and 15 mg lenalidomide cohorts, respectively) were enrolled (18 with DLBCL-NOS, and 2 with Burkitt-like lymphoma): 60% male, median age 58 (23–70) years. First-line treatment consisted of R-CHOP or similar in 18 patients and Burkitt’s lymphoma protocols in 2. Disease status at LR-ESHAP was: primary refractory disease in 13 patients (partial response [PR], n=7; and更多