(22nd August, 2014; Business Wire India); Celgene Corporation (NASDAQ:CELG) announced that results of a study evaluating the combination of REVLIMID® (lenalidomide) with rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate and prednisone (R-CHOP) in untreated diffuse large b-cell lymphoma (DLBCL) were published online ahead of print in the Journal of Clinical Oncology.
In a phase II, open label, single arm study, by Dr. Grzegorz Nowakowski of the Mayo Clinic, 64 patients with newly diagnosed, untreated, stage II-IV CD20 positive DLBCL received 25 mg of lenalidomide on days 1-10 with standard dose R-CHOP every 21 days for six cycles. All patients received pegfilgrastim on day two of each cycle and aspirin prophylaxis throughout. The primary endpoint was event-free survival (EFS) with secondary endpoints of progression free survival (PFS) and overall survival (OS). A one-stage binomial design was used to assess the efficacy and tolerability of REVLIMID with R-CHOP.
Of the 64 patients enrolled, 60 were eligible for response evaluation. In these patients, the overall response (OR) rate was 98% (59/60) with 80% (48/60) achieving a complete response (CR). The 24-month EFS, which was identical to PFS, and OS rates were 59% (48-74%) and 78% (68-90%), respectively (95% CI).
DLBCL molecular sub-type was determined by tumor immunohistochemistry (Hans algorithm) and classified as germinal center B-cell (GCB) vs. non-GCB. Additionally, 87 consecutive control patients from the Mayo Clinic Lymphoma Database who received conventional R-CHOP and who met the same inclusion criteria as R2CHOP treated patients were identified and analyzed for outcome based on DLBCL sub-types.
In the R-CHOP patients, 24-month progression-free survival (PFS) and OS were 28% vs. 64%, p<0.001 and 46% vs. 78%, p<0.001 in non-GCB patients vs. GCB patients, respectively. In patients treated with R2CHOP, the 24-month PFS and OS rates were 60% vs. 59%, p=0.83 and 83% vs. 75%, p=0.61 in non-GCB patients vs. GCB patients, respectively.
The most common grade 3 or higher adverse events in the study were neutropenia (87%), leukopenia (80%), thrombocytopenia (44%), anemia (16%) and febrile neutropenia (9%). Thrombosis was reported in one patient and there was one death in the study from perforation/sepsis.
“This study demonstrated that the addition of lenalidomide to conventional R-CHOP resulted in similar PFS rates and OS rates between sub-types,” said Dr. Nowakowski. “This is intriguing as patients with the non-GCB phenotype have traditionally experienced poorer outcomes. The results of this study support further evaluation of this regimen in this sub-type of DLBCL.”
The full manuscript of the publication can be found at http://jco.ascopubs.org/content/early/recent?home-right. Additionally, findings from a study on behalf of the Fondazione Italiana Linfomi evaluating lenalidomide plus R-CHOP21 in elderly patients with untreated DLBCL was published online ahead of print on May 13 in The Lancet (http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(14)70191-3/abstract)
These studies build upon multiple trials evaluating combinations of lenalidomide and rituximab across non-Hodgkin’s lymphoma subtypes and helps support a broad phase III program at Celgene investigating combinations including lenalidomide and rituximab.
In DLBCL, REMARC, the company’s phase III study of lenalidomide maintenance compared with placebo following R-CHOP therapy completed enrollment in the first quarter of 2014. Also, ROBUST (DCL-002), the company’s pivotal phase III study evaluating lenalidomide plus R-CHOP21, is planned to start enrollment in the first quarter of 2015. Celgene also commenced a collaboration with NanoString Technologies this year to develop a companion biomarker diagnostic for purposes of classifying patient subtypes in the study. Further, the Eastern Cooperative Oncology Group (ECOG) is also enrolling patients to a phase II study of R2CHOP compared with R-CHOP in untreated DLBCL.
In follicular lymphoma, the company expects to complete enrollment of RELEVANCE, its phase III study of lenalidomide plus rituximab compared with rituximab plus chemotherapy in patients with previously untreated disease in the second half of 2014. Additionally, enrollment began earlier this year for AUGMENT, a phase III, double-blind study of lenalidomide plus rituximab compared with rituximab plus placebo in relapsed or refractory patients. Finally, the company will investigate the optimal dose and schedule of this regimen through MAGNIFY, evaluating lenalidomide plus rituximab followed by rituximab maintenance in patients with follicular, marginal zone and mantle cell lymphoma.
REVLIMID is not approved for the treatment of patients with follicular lymphoma or diffuse large b-cell lymphoma.
