Lenalidomide plus R-CHOP21 in newly diagnosed diffuse large B-cell lymphoma (DLBCL): long-term follow-up results from a combined analysis from two phase 2 trials

Abstract

Lenalidomide-RCHOP (R2-CHOP21) has been shown to be safe and effective in patients with untreated diffuse large B-cell lymphoma (DLBCL). The aim of this analysis is to report long-term outcome and toxicities in newly diagnosed DLBCL patients who received R2-CHOP21 in two independent phase 2 trials, conducted by Mayo Clinic (MC) and Fondazione Italiana Linfomi (FIL). All patients received R-CHOP21 plus lenalidomide. Long-term progression-free survival (PFS), time to progression (TTP), overall survival (OS) and late toxicities and second tumors were analyzed. Hundred and twelve patients (63 MC, 49 FIL) were included. Median age was 69 years, 88% were stage III–IV. At a median follow-up of 5.1 years, 5y-PFS was 63.5%, 5y-TTP 70.1% and 5y-OS 75.4%; according to cell of origin (COO): 5y-PFS 52.8% vs 64.5%, 5y-TTP 61.6% vs 69.6% and 5y-OS 68.6% vs 74.1% in germinal center (GCB) vs non-GCB respectively. Four patients experienced grade 4–5 late toxicities. Grade ≤ 3 toxicities were infections (N = 4), thrombosis (N = 1) and neuropathy (N = 3). Seven seconds tumors were observed. Long-term follow-up demonstrates that R2-CHOP21 efficacy was maintained with high rates of PFS, TTP, and OS. Lenalidomide appears to mitigate the negative prognosis of non-GCB phenotype. Incidence of therapy-related secondary malignancies and late toxicities were low.

New agents and regimens for diffuse large B cell lymphoma

“…Meanwhile, lenalidomide could exert direct tumor toxicities via binding to cereblon to inhibit downstream NF-κB signaling [ 33 ]. Combination of lenalidomide and R-CHOP21 (R2-CHOP) seemed to provide benefits in several phase 2 studies, especially for the non-GCB and high-risk subgroups [ 34 ]. In REMARC study, for elderly patients responding to first-line R-CHOP, lenalidomide maintenance for 24 months prolonged PFS over placebo, although no OS benefit was found [ 35 ].…”

Subcutaneous Rituximab-MiniCHOP Compared With Subcutaneous Rituximab-MiniCHOP Plus Lenalidomide in Diffuse Large B-Cell Lymphoma for Patients Age 80 Years or Older

“…9 In combination with R-CHOP (R2-CHOP), lenalidomide has acceptable levels of toxicity and may mitigate the negative prognosis of the non-GCB phenotype. 7,[10][11][12][13][14] It has also been suggested that the clinical benefit of lenalidomide monotherapy in patients with DLBCL was more evident in the gene-expression profiling (GEP)-defined ABC population. 15 On the basis of these data, we designed a randomized phase III clinical trial to determine the tolerance and efficacy of the R2-miniCHOP regimen in comparison to R-miniCHOP in patients older than 80 years with newly diagnosed DLBCL.…”

CHEMOTHERAPY ACCORDING TO THE R-mNHL-BFM-90 PROTOCOL IN COMBINATION WITH LENALIDOMIDE AS THE FIRST LINE THERAPY IN PATIENTS WITH MUM1-POSITIVE DIFFUSIVE LARGE B-CELL LYMPHOMA AND FOLLICULAR LYMPHOMA GRADE 3B

“…А. Castellino и соавт. [15] опубликовали отдаленные результаты, доказывающие преимущества программы R2-CHOP, где в группе больных non-GCB-ДВККЛ 5-летняя БПВ и ОВ составили 64,5 и 74,1 %. В анализируемой группе у 88 % была диагностирована III-IV стадии заболевания, у 56 % IPI составил 4-5 баллов.…”

“…В ряде работ показана высокая эффективность применения монотерапии леналидомидом у больных с рецидивом и прогрессией АВС-ДВККЛ [9,10], а также в качестве первой линии в сочетании с ХТ по схеме R-CHOP [11][12][13][14][15].…”