Celgene International Sàrl announced data from multiple phase III studies evaluating the benefit/risk profile of REVLIMID were presented during the International Myeloma Workshop in Paris, France.

The updated results were from four phase III studies of REVLIMID (lenalidomide), either as continuous therapy following high-dose melphalan and autologous stem cell therapy, as continuous therapy following induction with melphalan, prednisone and lenalidomide in patients with newly diagnosed multiple myeloma, or as therapy with lenalidomide plus dexamethasone as induction followed by continuous lenalidomide therapy in patients with smoldering multiple myeloma. Also presented was a retrospective safety analysis of 11 Celgene-sponsored trials evaluating lenalidomide plus dexamethasone in relapsed/refractory multiple myeloma patients.

Updated data from a National Cancer Institute-sponsored phase III, controlled, double-blind, multi-centre study of newly diagnosed multiple myeloma patients who received autologous stem cell transplant, followed by maintenance therapy with either lenalidomide (n=231) or placebo (n=229) were presented by representatives of a network of researchers led by the Cancer and Leukaemia Group B (CALGB). The updated study data showed that as of April 2011, patients receiving continuous lenalidomide following ASCT demonstrated an overall survival rate of 90% (208/231) compared to 83% (190/229) for patients initially receiving placebo (unadjusted p=0.018), despite nearly 80% (86/110) of placebo patients crossing over to receive continuous lenalidomide at the time of the study unblinding in December 2009.

The most common grade 3-4 adverse events experienced by patients receiving lenalidomide or placebo in the study, respectively, were neutropenia (43% 89/208 vs. 9% 17/197), thrombocytopenia (13% 26/208 vs. 4% 7/197) and infections (16% 33/208 vs. 5% 11/197). There were no grade 5 haematologic adverse events. The rate of grade 5 non-haematologic adverse events was similar between the two arms of the study (1% 3/208 vs. 2% 3/197).

An increase in second primary malignancies (SPMs), mainly haematological malignancies, was observed in the treatment arm compared to the control arm. However, an event free survival analysis, where SPM was included as an event, in addition to death and progression, demonstrated that there was no significant impact of SPMs on the observed TTP or OS benefit.

The CALGB 100104 data are from an investigational study. REVLIMID does not have marketing approval for the treatment of patients with newly diagnosed multiple myeloma.

In a second cooperative-group study presented by researchers from the Intergroupe Francophone du Myelome (IFM), patients receiving maintenance lenalidomide (n=307) following autologous stem cell transplant and two cycles of lenalidomide consolidation achieved a median progression-free survival of 41 months, compared to 24 months for patients receiving placebo (n=307) (p<0.0001). This translated to a 50% reduction in the risk of disease progression.

Very good partial response rate (VGPR) improved from 58% to 67% with consolidation therapy (p<0.0001) and there was a trend toward overall survival at four years following randomization with 79% of patients receiving lenalidomide maintenance still alive compared to 73% of patients receiving placebo (p=0.8).

The most common grade 3-4 adverse events experienced by patients receiving lenalidomide or placebo in the study, respectively, were neutropenia (43% vs. 14%,), thrombocytopenia (12% vs. 6%) and infections (10% vs. 5%). In the study, 29 patients developed second primary malignancies including six patients who developed b-cell malignancies (ALL and Hodgkin's disease). Four of these patients are now in complete remission and two remain on lenalidomide therapy.

The IFM 0502 data are from an investigational study. REVLIMID does not have marketing approval for the treatment of patients with multiple myeloma following autologous stem cell transplant.

In a phase III Celgene-sponsored study of lenalidomide plus melphalan and prednisone followed by continuous lenalidomide (MPR-R) compared to lenalidomide plus melphalan and prednisone followed by placebo (MPR) or melphalan and prednisone followed by placebo (MP), an analysis of SPM rates was conducted..

An increase in haematological malignancies was observed in the treatment arm (MPR-R) compared to the control arm (MP). An event free survival analysis where SPM was included as an event, in addition to death and progression showed that the risk of SPM, death or disease progression at two years for patients receiving MPR-R is 48%. For patients receiving MP, the risk of SPM, death or disease progression at two years is 83%, In addition, there was no significant impact of SPM on the magnitude of the observed PFS benefit in the treatment arm.

In the safety population (the patients who received at least one dose of therapy on study), the most common grade 4 haematological adverse events in the MPR-R and MP groups, respectively, included neutropenia (36%, vs. 8%, MP), thrombocytopenia (13%, vs. 4%,) and anaemia (5%, vs. 1%,). Deep vein thrombosis (3% vs <1%) and fatigue (6% vs 3%) were observed. Grade 3 or 4 peripheral neuropathy was experienced by no patients in the MPR-R arm and 1% of patients in the MP arm.

The MM-015 data are from an investigational study. REVLIMID does not have marketing approval for the treatment of patients with NDMM.

Also presented at the conference were updated results from a phase III randomized, multicenter study of lenalidomide plus dexamethasone as induction therapy followed by continuous lenalidomide therapy versus no treatment in patients with smoldering multiple myeloma.

After 9 cycles of induction therapy with lenalidomide and dexamethasone, the overall response rate was 81% on an intent to treat basis (n=57) including 8% complete response (CR), 8% stringent complete response (sCR) and 12% very good partial response (VGPR). Patients receiving a median of 6 cycles of continuous lenalidomide (1-21, n=50) saw sCR rates increase to 12%. Time to progression from inclusion was 25 months in the no treatment arm and the median TTP was not reached in the treatment arm (p=0.0001) (HR: 6.2; 95% CI = 2.-15). After a median follow-up of 22 months, 6 patients receiving continuous lenalidomide had progressed to active disease and 12 patients had developed biological progression but with the addition of dexamethasone, the disease remained controlled. In the no treatment arm, 28 of 61 patients progressed to active multiple myeloma.

At a median follow-up of 29 months, the 5-year overall survival rate of patients in the treatment arm was 98% compared to 87% in the no treatment arm (p=0.03).

One patient in the treatment arm was diagnosed with prostate cancer 16 months after inclusion, however the patient had a history of elevated PSA levels prior to study entry. A second patient, who was diagnosed with polycythaemia vera 17 months after inclusion and was identified as Jak 2+ at randomization.

These data are from an investigational study. REVLIMID does not have marketing approval for the treatment of patients with smoldering multiple myeloma.

In a separate presentation, data from lenalidomide-based arms in 11 Celgene-sponsored studies of patients with relapsed/refractory multiple myeloma were retrospectively analyzed for the incidence of SPMs.

The incidence rate in this analysis of 3,846 patients was 2.08 per 100 patient years. According to the study, these incidence rates are similar to the incidence rate (2.1 per 100 patient years for patients > 65 years old) of developing cancer in the background population, (U.S. SEER Cancer Registry data). Additionally, the incidence rate of SPM in patients who received more than 24 months of therapy (n=313), 2.35 per 100 patient years, was also similar to the background population and no patients developed b-cell malignancies.

REVLIMID is an IMiDs compound. REVLIMID and other IMiDs continue to be evaluated in over 100 clinical trials. The IMiDs pipeline is covered by a comprehensive intellectual property estate of issued and pending patent applications in the US, EU and other regions, including composition-of- matter and use patents.

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 Americas, the Middle-East and Asia for transfusion-dependent anaemiaa due to low- or intermediate-1-risk MDS associated with a deletion 5q cytogenetic abnormality with or without additional cytogenetic abnormalities. Marketing Authorization Applications are currently being evaluated in a number of other countries.

Celgene International Sàrl, located in Boudry, in the Canton of Neuchâtel, Switzerland, is a wholly owned subsidiary and international headquarters of Celgene Corporation. Celgene Corporation, headquartered in Summit, New Jersey, is an integrated global pharmaceutical company engaged primarily in the discovery, development and commercialization of innovative therapies for the treatment of cancer and inflammatory diseases through gene and protein regulation.