Celgene International Sàrl (NASDAQ: CELG) announced that data from multiple studies presented at the 14th Congress of the European Society of Hematology demonstrate that REVLIMID provides powerful and sustained responses in patients with multiple myeloma.
These key presentations support the advantage of active long-term disease control along with manageable safety profiles, leading to unprecedented survival times.
“Together, the studies presented at this congress demonstrate that the use of REVLIMID early on in the course of the disease allows for rapid and durable responses that lead to the best survival benefits we’ve seen yet for this patient population,” said Jean-Pierre Bizzari, Senior Vice President and Group Head of Global Oncology/Hematology for Celgene. “We are excited that the dual mode of action of REVLIMID, which includes both a direct killing effect against myeloma cells and a unique immune-enhancing effect, controls and manages the disease over the long-term.”
Speed of response with lenalidomide and dexamethasone in patients with relapsed or refractory multiple myeloma: First results of the MM-019 German compassionate use protocol
Treatment time required for patients with multiple myeloma to respond to therapy with REVLIMID plus dexamethasone was examined in a phase IIIb, open-label, non-comparative trial. Patients had received at least one previous therapy and were treated in 28-day courses that were repeated until disease progression, toxicity or withdrawal by the physician or patient.
Patients’ previous therapies, including transplantations, bortezomib and thalidomide, did not influence response rates. Fifteen patients (12%) had been previously treated with all three regimens, 43 (35%) with two and 42 (34%) with one.
Best response information, measured by levels of M protein and free light chains (FLC), was available for 113 patients, including four patients with a complete response, 80 with a partial response, 28 with stable disease and one with disease progression.
Time to a 50 percent reduction in M-protein or FLC was analysed for 122 patients. For responding patients, median time to response was 28 days, with 39 percent of patients seeing a response in two weeks.
“These data demonstrate that nearly three-quarters of patients achieved a partial response or better, despite having been heavily pretreated,” said Dr. Katja Weisel of University Hospital in Tübingen, Germany. “The responses were rapid, with half of the patients responding well within the first treatment course.”
Longer duration of treatment and maintenance of best response with lenalidomide plus dexamethasone increases overall survival (OS) in patients with relapsed/refractory multiple myeloma
A subset analysis of updated, pooled data from the MM-009/MM-010 international phase III trials demonstrated a survival benefit upon continued treatment with REVLIMID® plus dexamethasone after achieving best clinical response in patients with relapsed or refractory multiple myeloma.
Survival estimates for patients achieving a partial response or better were compared between patients on continuous treatment (those still undergoing treatment or who discontinued due to disease progression) and patients who discontinued treatment early due to adverse events, consent withdrawal or other reasons. Median follow-up time for surviving patients was 48 months.
The estimated median survival time for patients continuing treatment after achieving a partial response or better (N=174) was 50.9 months [95% confidence interval: 43.0-NR], while the median survival time for those who discontinued treatment early (N=38) was 34.95 months [26.4-55.7; P=0.0594].
When differences in the groups’ patient characteristics (such as age, number of prior treatments, etc.) were also taken into account, the group that continued treatment had significantly better survival outcomes than did the group that discontinued therapy.
The number of patients who discontinued early due to adverse events was low (N=22, 10%).
“This study suggests that therapy with REVLIMID plus dexamethasone should be prolonged even after the patient achieves an initial response,” concluded Dr. Jesus San Miguel of the University Hospital of Salamanca in Salamanca, Spain. “The lasting effects gained by additional rounds of treatment may significantly prolong survival for these patients.”
Lenalidomide-based therapy leads to improvement in humoral immune system in relapsed or refractory multiple myeloma patients who respond to the therapy
Dr. Rachid Baz of the Moffitt Cancer Center & Research Institute, in Tampa, FL, USA presented another analysis of MM-009/MM-010, as well as of a large phase II study of REVLIMID® as a single agent therapy in patients with relapsed or refractory multiple myeloma, demonstrated that REVLIMID therapy improves patient immunity by boosting immunoglobulin A (IgA) levels.
Levels of IgA, an important antibody for fighting infections, are commonly reduced in patients with multiple myeloma. These low levels are associated with recurrent bacterial infections – the most common cause of death for patients in advanced stages of the disease.
The study measured baseline levels of the antibodies and evaluated antibody responses to therapy on a monthly basis. Improvement was defined as an increase in antibody levels to at least the lower limit of normal and a 25 percent increase in value.
Only patients who responded to therapy showed significant improvement and normalisation of residual IgA levels. At baseline, residual IgA levels were normal in 30 and 17 percent of responders in MM-009/MM-010 and MM-014, respectively. With treatment, normalised IgA levels were found in 56 percent of responders in MM-009/MM-010 by cycle seven and in 50 percent of responders in MM-014 by cycle five.
Patients whose IgA levels normalised had significantly longer progression-free (29-77 weeks) and overall (121-220 weeks) survival times compared to those whose IgA levels did not improve (P=0.0001).
Lenalidomide in combination with dexamethasone at first relapse in comparison with its use as later salvage therapy in relapsed or refractory multiple myeloma
Also of note is a study that was recently published in the European Journal of Hematology. This subset analysis of MM-009/MM-010 demonstrated the benefit of initiating REVLIMID plus dexamethasone at first relapse compared to later salvage therapy.
The study showed that, with REVLIMID plus dexamethasone, patients who had received one prior therapy demonstrated significant improvements compared to those who had received two or more prior therapies in outcomes such as median time to disease progression (17.1 vs. 10.6 months; P=0.026), median progression-free survival (14.2 vs. 9.5 months; P=0.047), complete or very good partial responses (39.8% vs. 27.7%; P=0.025) and median overall survival (42.0 vs. 35.8 months; P=0.041).
“These results suggest that it may be beneficial to patients to be treated with REVLIMID plus dexamethasone earlier on in the treatment course,” said Dr. Edward A. Staudtmauer of the Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA. “Based on the findings, the combination of REVLIMID and dexamethasone should be considered as a second-line therapy for patients with multiple myeloma.”
REVLIMID® is approved in the United States, Canada, Argentina, Peru, Bolivia and Columbia, as well as Malaysia and Israel, for transfusion-dependent anemia due to low- or intermediate-1-risk MDS associated with a deletion 5q cytogenetic abnormality with or without additional cytogenetic abnormalities, with Marketing Authorisation Applications currently being evaluated in a number of other countries. REVLIMID has obtained Orphan Drug Designation in MDS in the United States, European Union, Switzerland and Australia.
REVLIMID is also approved in the United States, the European Union, Canada, Argentina, Peru, Bolivia, Columbia, Guatemala, Switzerland, Malaysia, Israel, Singapore and Russia in combination with dexamethasone for the treatment of patients with multiple myeloma who have received at least one prior therapy and in Australia and New Zealand in combination with dexamethasone for the treatment of patients whose disease has progressed after one therapy.
REVLIMID is an IMiDs® compound, a member of a proprietary group of novel immunomodulatory agents. REVLIMID and other IMiDs compounds continue to be evaluated in over 100 clinical trials in a broad range of oncological conditions, both in blood cancers and solid tumors. The IMiDs pipeline is covered by a comprehensive intellectual property estate of issued and pending patent applications including composition-of- matter and use patents.
About Multiple Myeloma
Multiple myeloma (also known as myeloma or plasma cell myeloma) is a cancer of the blood in which malignant plasma cells are overproduced in the bone marrow. Plasma cells are white blood cells that help produce antibodies called immunoglobulins that fight infection and disease. However, most patients with multiple myeloma have cells that produce a form of immunoglobulin called paraprotein (or M protein) that does not benefit the body. In addition, the malignant plasma cells replace normal plasma cells and other white blood cells important to the immune system. Multiple myeloma cells can also attach to other tissues of the body, such as bone, and produce tumors. The cause of the disease remains unknown.
About Celgene International Sàrl
Celgene International Sàrl, located in Boudry, 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. For more information, please visit the Company’s website at www.celgene.com.
REVLIMID® is a registered trademark of Celgene Corporation.
This release contains certain forward-looking statements which involve known and unknown risks, delays, uncertainties and other factors not under the Company’s control, which may cause actual results, performance or achievements of the Company to be materially different from the results, performance or other expectations implied by these forward-looking statements. These factors include results of current or pending research and development activities, actions by the FDA and other regulatory authorities, and those factors detailed in the Company’s filings with the Securities and Exchange Commission such as Form 10-K, 10-Q and 8-K reports.