Response of relapsed/refractory diffuse large B-cell lymphoma (DLBCL) with nongerminal center B-cell phenotype to lenalidomide (L) alone or in combination with rituximab (R).

Abstract

8038 Background: Novel salvage therapies for relapsed/refractory (r/r) DLBCL and the identification of specific biomarkers predictive of response to a specific therapy are needed. L has an overall response rate (ORR) of 28% in r/r DLBCL. Methods: We retrospectively evaluated differences in clinical outcomes for germinal center B-cell (GCB)-like vs non-GCB-like DLBCL patients treated with salvage L alone (RPCI) or L+R (DHOS-S). We are augmenting the current database with pathology specimens from r/r DLBCL patients treated with L monotherapy at the Mayo Clinic and Hackensack Cancer Center. The initial data set from RPCI included 18 patients with r/r large cell lymphoma: 8M/10F; median age: 64 yrs; median 4 prior treatments. Patients were classified as GCB (n=9) or non-GCB (n=9) using the Hans criteria. Differences in overall response rate (ORR), CR or PR rates, progression-free survival (PFS), and overall survival (OS) were compared between GCB and non-GCB DLBCL. Results: No differences in stage, international prognostic index (IPI) score, prior number of treatments, were noted between the two groups. A significant difference in clinical response to L was observed: ORR was 77% for non-GCB patients vs 11% for GCB patients (P=0.011); and 44% of non- GCB patients achieved a CR vs 11% of patients with the GCB phenotype. PFS for patients with the non-GCB subtype was 336 days vs 72 days for patients with the GCB subtype (P=0.008). Although, median OS for the non-GCB subgroup was 420+ days compared with 73 days for GCB patients, it did not reach statistical significance (P=0.4). In a separate analysis, an additional 8 patients with r/r DLBCL (all non-GCB subtype), treated at the DHOS-S with L+R, achieved an ORR of 50%. This appears to be favorable relative to historical controls. Conclusions: Our data suggests that these two subgroups of patients with DLBCL (i.e. GCB vs non-GCB) appear to have a significantly different response to L in the r/r setting. Results from the analysis of the expanded data set are anticipated in time for the congress, and a large international trial is in development in an attempt to prospectively validate our findings. No significant financial relationships to disclose.