Xiya Reagent:Age, Renal Impairment and Depth of Response Analyse

Age, Renal Impairment and Depth of Response Analyses of the First (MM-020/IFM 07-01) Study of Continuous REVLIMID® (lenalidomide) Plus Low-Dose dexamethasone in Newly-Diagnosed Multiple Myeloma Presented at ASH

Continuous REVLIMID® (lenalidomide) plus low-dose dexamethasone increased progression-free survival compared with fixed duration of Rd or melphalan, prednisone and thalidomide regardless of age, renal impairment, or depth of response

SAN FRANCISCO--(BUSINESS WIRE)-- Celgene Corporation (NASDAQ:CELG) today announced that results were presented from multiple post-hoc analyses of its pivotal phase III FIRSTTM (MM-020/IFM 07-01) trial, comparing continuous REVLIMID® (lenalidomide) plus low-dose dexamethasone (continuous Rd) to a fixed duration of 18 cycles of Rd (Rd18) or 12 cycles of melphalan, prednisone and thalidomide (MPT) for the treatment of newly diagnosed, transplant-ineligible multiple myeloma. The studies were presented during the 56th American Society of Hematology (ASH) annual meeting.

As previously reported, the study met the primary endpoint of progression-free survival (PFS) in the intent-to-treat analysis of all randomized patients (Median PFS 21.2 months MPT vs 25.5 months Rd, Hazard Ratio (HR) 0.72, p < 0.01).

In one analysis, the authors examined the impact of age (75 years or younger vs. over 75 years) on PFS and secondary endpoints. Overall, 35% of patients were over 75 years of age.

PFS and overall survival (OS) outcomes favored continuous Rd over MPT and over Rd18 in both age groups.

In addition, response rates were higher with continuous RD vs MPT and duration of response was longer in the continuous Rd arm compared to MPT in both age groups.

"These analyses continue to validate the published data for certain older patients receiving continuous therapy with lenalidomide and dexamethasone compared to a standard triplet regimen," said Prof. Thierry Facon, MD, University of Lille and primary investigator of the study.

Additionally, an analysis of patients with renal impairment (RI) was presented. In the study, 24% had normal renal function (creatinine clearance [CrCl] ≥ 80 mL/min), 44% presented with mild RI (CrCl ≥ 50 and < 80 mL/min), 23% had moderate RI (CrCl ≥ 30 and < 50 mL/min), and 9% had severe RI (CrCl < 30 mL/min). Patients requiring dialysis were excluded. The starting doses of lenalidomide (25 mg for pts with normal renal function or mild RI, 10 mg QD for moderate RI, and 15 mg every other day for severe RI) in the Rd arms and of melphalan (reduced by 50% in patients with moderate or severe RI) in the MPT arm were adjusted for patients with CrCl < 50 mL/min.

Continuous Rd demonstrated a longer PFS compared with MPT in all groups of patients with renal impairment, in particular, in patients with normal renal function (HR = 0.71; P = 0.05), in patients with mild RI (HR = 0.74; P = 0.02), patients with moderate RI (HR = 0.66; P < 0.01) and in patients with severe RI (HR 0.76; P=0.31). A slight PFS benefit was also seen with continuous Rd compared to Rd18 (a secondary comparison) in patients with mild or moderate RI (P < 0.01 for both).

An analysis of the impact of depth of response on PFS was also presented. In patients who achieved at least a very good partial response (VGPR), median PFS was significantly longer (not reached (NR) with continuous Rd compared with Rd18 (31.0 months; HR = 0.46; P < 0.01) or MPT (34.7 months; HR = 0.55; P < 001). A benefit of continuous Rd was observed compared with Rd18 or MPT in patients who achieved a complete response (CR), where the median PFS with continuous Rd was NR vs. 45.2 months with Rd18 (HR = 0.29; P < 0.01) and 44.6 months with MPT (HR = 0.28; P < 0.01).

Safety results in the FIRST study (N Engl J Med 2014) showed that grade 3/4 adverse events that occurred in at least 8% of patients in the continuous Rd arm, Rd18 arm or MPT arm included neutropenia (28%, 26% and 45%, respectively), anemia (18%, 16% and 19%, respectively), thrombocytopenia (8%, 8% and 11%, respectively), febrile neutropenia (1%, 3% and 3%, respectively), leukopenia (5%, 6% and 10%, respectively), infection (29%, 22% and 17%, respectively), pneumonia (8%, 8% and 6%, respectively), deep-vein thrombosis and/or pulmonary embolism (8%, 6% and 5%, respectively), asthenia (8%, 6% and 6%, respectively), fatigue (7%, 9% and 6%, respectively), and peripheral sensory neuropathy (1%, < 1% and 9%, respectively). Rates of grade 3/4 cardiac disorders for patients in the continuous Rd, Rd18 and MPT arms were 12%, 7% and 9%, respectively. The incidence of invasive second primary malignancies was 3% in patients taking continuous Rd, 6% in patients taking Rd18 and 5% in patients taking MPT. The overall incidence of solid tumors was identical in the continuous Rd and MPT arms (3%) and 5% in the Rd18 arm.

Celgene has submitted applications for approval of REVLIMID in combination with dexamethasone for the treatment of newly diagnosed multiple myeloma patients with the European Medicines Agency (EMA) in February 2014 and with the U.S. Food and Drug Administration (FDA) in April 2014. The U.S. Food and Drug Administration has set a Prescription Drug User Fee Act (PDUFA) date of Feb. 22, 2015.

REVLIMID plus low-dose dexamethasone is not indicated for the treatment of newly diagnosed multiple myeloma in any country.

About REVLIMID®

REVLIMID is approved in combination with dexamethasone for the treatment of patients with multiple myeloma who have received at least one prior therapy in nearly 70 countries, encompassing Europe, the Americas, the Middle-East and Asia, and in combination with dexamethasone for the treatment of patients whose disease has progressed after one therapy in Australia and New Zealand.

REVLIMID is also approved in the United States, Canada, Switzerland, Australia, New Zealand and several Latin American countries, as well as Malaysia and Israel, for transfusion-dependent anaemia due to low- or intermediate-1-risk MDS associated with a deletion 5q cytogenetic abnormality with or without additional cytogenetic abnormalities and in Europe for the treatment of patients with transfusion-dependent anemia due to low- or intermediate-1-risk myelodysplastic syndromes associated with an isolated deletion 5q cytogenetic abnormality when other therapeutic options are insufficient or inadequate.

In addition, REVLIMID is approved in the United States for the treatment of patients with mantle cell lymphoma (MCL) whose disease has relapsed or progressed after two prior therapies, one of which included bortezomib.· 以上资料由西亚试剂：http://www.xiyashiji.com/ 提供此产品的详细信息如密度,含量,分子式,分子量等均可在西亚官网查询