Date: 2014-12-08
Type of information: Presentation of results at a congress
phase: 2-3
Announcement: presentation of results at the 56th American Society of Hematology (ASH) Annual Meeting and Exposition, being held December 6-9 in San Francisco, CA
Company: Celgene (USA - NJ)
Product: Revlimid® (lenalidomide)
Action mechanism:
Disease: relapsed/refractory diffuse large B-cell lymphoma (DLBCL)
Therapeutic area: Cancer - Oncology
Country:
Trial
details: This randomized, multicenter, open-label, phase II/III study was conducted to determine the efficacy and safety of single-agent lenalidomide vs. single-agent investigator\'s choice (IC) in relapsed/refractory DLBCL patients who received at least two prior therapies, or were ineligible for stem cell transplantation or further combination chemotherapy. DLBCL subtype (GCB vs non-GCB) was determined by a central pathology lab using immunohistochemistry (IHC) per the Hans method (Hans 2004). Patients were stratified by subtype, then randomized 1:1 to receive lenalidomide (25 mg/day, 21 days of 28-day cycle) or IC (gemcitabine, rituximab, etoposide, or oxaliplatin) until progressive disease (PD), unacceptable toxicity, or voluntary withdrawal. In the event of radiologically confirmed PD, patients in the IC arm were allowed to cross over to lenalidomide. The primary endpoint for Stage 1 was overall response rate (ORR), as determined by an Independent Response Assessment Committee. Progression-free survival (PFS), overall survival (OS) and subtype analysis using gene expression profiling (GEP) were exploratory endpoints. Concordance of GEP and IHC was evaluated from three separate laboratories. Prespecified criterion to advance to Stage 2 was a two-sided 15 percent significance level in ORR in favor of lenalidomide based on IHC-defined subtype. The data did not fulfill this requirement, and stage 2 was not opened.
Latest
news: * On December 8, 2014, Celgene announced that results were presented from a phase II/III study (DLC-001) of Revlimid® (lenalidomide) compared with investigators\' choice (IC) of therapy in patients with relapsed/refractory diffuse large b-cell lymphoma (DLBCL) were presented during the 56th American Society of Hematology annual meeting. In this study, presented by Myron Czuczman, M.D., the data suggest improved response rates, progression-free survival and overall survival with lenalidomide compared with IC in the non-germinal b-cell (GCB) population as defined by immunohistochemistry (IHC). These improved outcomes appeared more pronounced in the activated b-cell (ABC) sub-type when assessed by gene expression profiling.
Patients with both GCB and ABC DLBCL sub-types treated with lenalidomide had a similar overall response rate, but significant progression-free survival (PFS) and overall survival (OS) compared to IC.
Patients with GCB DLBCL treated with lenalidomide had an ORR of 26.1% (n=23/102; p=.279) compared to 28.6% in non-GCB DLBCL patients treated with lenalidomide (n=28/102; p=.179) per IHC. The data suggested greater improvements in PFS and OS with lenalidomide (15.1 weeks PFS; p=.021; HR 0.50 [CI 95%, 0.27-0.92]; 32.3 weeks OS; p=.253; HR 0.70 [CI 95%, 0.38-1.30]) compared to IC (7.1 weeks PFS; p=.021; HR .50 [CI 95%, 0.27-0.92]; 20.4 weeks OS; p=.253; HR 0.70 [CI 95%, 0.38-1.30]) in the non-GCB patients. Patients in the ABC subtype as defined by GEP had improved ORR of 45.5% (n=11/102; p=.206) compared to 18.8% in those treated with IC (n=16/102; p=.206). There were also significantly improved PFS rates in the ABC subtype of patients treated with lenalidomide versus IC (82.0 weeks PFS vs. 6.2 weeks PFS, respectively; p=.105; HR 0.44 [CI 95%, 0.15-1.23]) as well as OS rates (108.4 weeks vs. 18.6 weeks; p=.144; HR 0.47 [CI 95%, 0.17-1.33]).
All patients, regardless of subtype or therapy group, experienced one or more treatment-emergent adverse event, with neutropenia, anemia, and thrombocytopenia being the most common.
Based on the results of this study, Celgene will open the ROBUST study evaluating lenalidomide plus rituximab, cyclophosphamide, doxorubicin, prednisone and vincristine (R2CHOP) compared with placebo plus R-CHOP in patients who have untreated ABC-type DLBCL. The study will utilize GEP subtyping through Celgene\'s collaboration with NanoString Technologies.
