Higher response to lenalidomide in relapsed/refractory diffuse large B‐cell lymphoma in nongerminal center B‐cell–like than in germinal center B‐cell–like phenotype

Abstract

BACKGROUND: There is a need to develop novel therapies for relapsed/refractory diffuse large B-cell lymphoma (DLBCL) and to identify biomarkers predictive for therapeutic response. Lenalidomide was previously shown to induce an overall response rate (ORR) of 28% in patients with relapsed/refractory DLBCL. It is currently unknown if response rates differ between patients with different DLBCL subtypes. METHODS: The authors retrospectively evaluated clinical outcomes of patients with germinal center B-cell-like versus nongerminal center B-cell-like DLBCL treated with salvage lenalidomide at 4 academic institutions. RESULTS: Forty patients with relapsed/refractory DLBCL were included (24 men; 16 women; median age, 66 years; median of 4 prior treatments, including rituximab chemotherapy). Patients were classified as germinal center B-cell-like (n ¼ 23) or nongerminal center B-cell-like (n ¼ 17) DLBCL according to the Hans algorithm. The subgroups were similar in terms of stage, international prognostic index score, prior number of treatments, and rituximab resistance. A significant difference in clinical response to lenalidomide was observed in nongerminal center B-cell-like versus germinal center B-cell-like patients. ORR was 52.9% versus 8.7% (P ¼ .006); complete response rate was 23.5% versus 4.3%. Median progression-free survival was 6.2 versus 1.7 months (P ¼ .004), although no difference in OS was observed between nongerminal center B-cell-like and germinal center B-cell-like DLBCL patients. CONCLUSIONS: The data suggest that the 2 major subgroups of patients with DLBCL (germinal center B cell and nongerminal center B cell) have different antitumor responsiveness to lenalidomide in the relapsed/refractory setting. A large international trial (NCT01197560) has been opened to enrollment in an attempt to prospectively validate these retrospective observations. Cancer 2011;117:5058-

The Hans algorithm failed to predict outcome in patients with diffuse large B-cell lymphoma treated with rituximab

“…Several papers have been published demonstrating the different efficacy of bortezomib in combination with chemotherapy in patients with ABC vs. GCB lymphoma [9]. Similarly, the efficacy of lenalidomide in monotherapy has been demonstrated as significantly different in nonGC vs. GC subtype [10]. GEP however still requires the availability of fresh (frozen) material and is rather expensive.…”

“…This algorithm was based on the immunohistochemical expression of CD 10, bcl-6 and MUM 1 proteins. Over the years, a number of papers have been published, some of which confirm the prognostic division according to Hans [8,[10][11][12][13] while others failed to find statistically significant differences between these two groups [14][15][16][17][18].…”

EBV‐positive diffuse large B‐cell lymphoma of the elderly: 2016 update on diagnosis, risk‐stratification, and management

“…Lenalidomide can also target the ABC DLBCL by down regulating interferon regulatory factor (IRF4) and the NF-kB pathway [46]. Early clinical data showed preferential activity in refractory/relapsed ABC vs. GCB DLBCL, with an overall response rate (ORR) of 53% and 9%, respectively [47]. Given these results, two studies adding lenalidomide to R-CHOP in newly diagnosed DLBCL have recently been completed [48,49].…”

Lenalidomide plus cyclophosphamide, doxorubicin, vincristine, prednisone and rituximab is safe and effective in untreated, elderly patients with diffuse large B-cell lymphoma: a phase I study by the Fondazione Italiana Linfomi

“…Furthermore, a recent study suggests that lenalidomide has improved activity in activated B-cell-like DLBCL compared with germinal center B-cell-like DLBCL. 39 This issue is a point of interest and an analysis of it is planned in the phase II part of this trial. Two prior phase I studies of LR-CHOP provided initial evidence of clinical activity and good tolerability in patients with advanced untreated DLBCL and FL, but this was in a population not restricted to elderly patients.…”