Celgene International Sàrl, a wholly-owned subsidiary of Celgene Corporation (NASDAQ:CELG) today announced that results from two studies of REVLIMID (lenalidomide) combinations in patients with diffuse large B-cell lymphoma (DLBCL) were presented at the American Society of Hematology annual meeting in New Orleans, La.
In the first study, Dr. Nishitha M. Reddy evaluated whether maintenance treatment with lenalidomide plus rituximab would result in a clinically significant reduction in relapse rates when compared with lenalidomide alone. DLBCL patients with an intermediate/high to high-risk international prognostic index (IPI) are at an increased risk of disease relapse rate in the first year after completion of standard therapy with R-CHOP.
Forty-four intermediate-high/high risk IPI patients were randomized to receive either lenalidomide at a dose of 25 mg daily for 21 days of 28 days (Arm A>
At a median follow up of 28.3 months, the 2-year disease-free survival (DFS) and overall survival (OS) were 86% and 84%, respectively. For patients in arm A and arm B the 2-year DFS was 90% vs. 82% and the 2-year OS was 96% vs. 72%, respectively>
Adverse events with patients experiencing grade 3-4 toxicities included neutropenia (23%), fatigue (13%), hypothyroidism (4%), DVT (2%), rash (2%) and febrile neutropenia (3%). Related grade 1-2 toxicities include hypothyroidism (13%) and rash (45%).
The results of this study showed that lenalidomide as maintenance therapy demonstrated clinical activity following standard chemotherapy in DLBCL patients with high risk prognostic features.
Dr. Annalisa Chiappella presented results from a second study of lenalidomide, this one in treatment-naïve, elderly DLBCL patients. The study investigated whether lenalidomide added to a chemotherapy plus rituximab (RCHOP21) regimen would improve overall response rate (ORR) compared to historical results with standard RCHOP21.
The author reports that the standard treatment for elderly untreated DLBCL is RCHOP21, however up to 40% of patients experience failures. In this phase II study, 49 patients were enrolled and given RCHOP21 plus 15 mg lenalidomide (R2CHOP21) from day 1 to 14 for 6 courses. Improvement in ORR was the primary endpoint. All cases were centrally reviewed by an expert pathologist.
At the end of 6 cycles of R2CHOP21, ORR was 92%, complete response rate (CR) was 86% and partial response rate (PR) was 6%. At a median follow-up of 28 months, 2-year OS was 92% (95% CI: 79-97), 2-year progression-free survival (PFS) was 80% (95% CI: 64-89) and 2-year event-free survival (EFS) was 70% (95% CI: 55-81). The 2-year PFS for International Prognostic Index (IPI) low-intermediate risk, intermediate-high risk, and high-risk patients was 89% (95% CI: 62-97), 76% (95% CI: 47-90), and 72% (95% CI: 36-90), respectively.
Hematological and extra-hematological toxicities were mild, with no grade IV extra-hematological events and no toxic deaths during treatment.
In the study presented by Dr. Chiappella, the ORR for GCB and non-GCB sub-types were 88% (CR 81%) and 88% (CR 88%), respectively. At a median follow-up of 28 months, 2-year PFS was 71% (95% CI: 40-88) in the GCB-group and 81% (95% CI: 51-93) in non-GCB-group.
The R2CHOP21 results in poor-risk, elderly patients, particularly in non-GC subgroups, warrant a phase III randomized trial comparing R2CHOP21 vs. RCHOP21 in untreated non-GCB DLBCL patients.
Finally, Dr. Elise Chong presented results from a study of the combination of lenalidomide and rituximab in indolent or mantle cell lymphoma. The study investigated whether the combination of lenalidomide plus rituximab would improve response rates in patients previously treated with rituximab therapy.
In the study, 42 patients with indolent or mantle cell lymphomas who were resistant, refractory or who had relapsed while on rituximab-containing regimens were enrolled and given two 28-day treatment cycles of lenalidomide 10 mg every day and dexamethasone 8 mg once weekly. After an assessment of response to this phase, all patients received four weekly doses of rituximab 375 mg/m2 during cycle 3 in addition to the lenalidomide and dexamethasone treatment. Lenalidomide and dexamethasone were continued in stable and responding patients until disease progression or development of clinically unacceptable toxicity. Improvement in response was the primary endpoint. All cases were centrally reviewed by an expert pathologist.
The response rate for all patients evaluable for response>
The most common grade 3-4 adverse events included neutropenia (48%), hypokalemia (12%), hypophosphatemia (8%), rash (6%), tumor flare (4%) and gastrointestinal complaints (4%).
REVLIMID® is not indicated for the treatment of patients with diffuse large B-cell lymphoma in any country.
Celgene International Sàrl