Results from two large international studies showed that patients with relapsed or refractory multiple myeloma, a cancer of the cells in the bone marrow that make blood, who were treated with Revlimid (lenalidomide) and dexamethasone had significantly improved progression-free and overall survival compared with patients treated with dexamethasone and placebo.
The trials took place in North America and Europe and are reported in the November 22nd issue of the New England Journal of Medicine (NEJM).
Both the studies showed that patients treated with the lenalidomide and dexamethasone had an overall response rate of over 60 per cent compared with around 20 per cent for patients on the dexamethasone and placebo arm. Also, results showed that patients on the combination drug arm had a 30 per cent greater overall survival and more than twice the time to progression of the dexamethasone and placebo patients.
One of the universities that took part in the North American study was Rush University Medical Center, based in Chicago, Illinois. Director of the Hematology section at the university, Dr Stephanie Gregory said:
“Myeloma, also called multiple myeloma, is of growing interest and concern.”
“Statistics show the number of diagnoses is increasing in the United States where most cancers are decreasing, and myeloma is being found in increasingly younger patients. These trends give us some urgency in having potent treatments to fight this disease,” she added.
Lenalidomide is a more potent analogue of thalidomide and is marketed as Revlimid, by the Celgene Corporation. It belongs to a class of drugs known as immunomodulatory agents because they change the way the immune system works.
The drug has attracted attention because it’s part of a new range of therapies that has dramatically changed quality of life for myeloma patients. It’s an oral drug that can be taken at home, and it does not have the difficult side effects of conventional chemotherapies because it directly targets cancer cells and the processes that help them grow.
In the North American trial, which took place in Canada and the US, 353 patients who had received at least one previous therapy for multiple myeloma were randomly assigned to receive lenalidomide or placebo. Both groups also received dexamethasone. The drugs were administered in a different daily pattern based on several 28-day cycles. The researchers monitored safety, clinical response, time to progression, and overall survival.
The results showed that the lenalidomide group had a 61 per cent overall response rate compared with 19.9 per cent in the placebo group, and the groups showed a complete response rate of 14.1 and 0.6 per cent respectively.
Median overall survival was 29.6 months for the lenalidomide group compared with 20.2 for the placebo group, and median time to progression was 11.1 months and 4.7 months respectively.
Grade 3 or 4 adverese events were spotted in 85.3 per cent of the lenalidomide group and 73.1 per cent of the placebo group. These events led to 19.8 and 10.2 per cent of patients discontinuing in the respective groups.
Grade 3 or 4 neutropenia and venous thromboembolism were more prevalent in the lenalidomide than the placebo group (41.2 versus 4.6 per cent, and 14.7 versus 3.4 per cent respectively).
The study concluded that:
“Lenalidomide plus dexamethasone is superior to placebo plus dexamethasone in patients with relapsed or refractory multiple myeloma.”
The European study was led by the University of Athens, and enrolled 351 participants in a similar research design where each participant was randomly assinged to receive either lenalidomide and dexamethasone or placebo plus dexamethasone. The researchers monitored just time to progression in this study.
The results showed similar patterns to the North American study, with time to progression being significantly longer for the lenalidomide group than for the placebo group: 11.3 months versus 4.7 months respectively.
The overall response rate was 60.2 per cent in the lenalidomide group and 24 per cent in the placebo group, and complete responses occurred in 15.9 per cent of the lenalidomide group compared with 3.4 per cent of the placebo group. The lenalidomide group also had a 34 per cent improvement in overall survival compared to the placebo group.
Grade 3 or 4 adverse events that were spotted in more than 10 per cent of the lenalidomide participants were neutropenia (29.5 versus 2.3 per cent in the placebo group), thrombocytopenia (11.4 versus 5.7 per cent in the placebo group), and venous thromboembolism (11.4 versus 4.6 per cent).
The researchers in the European study came to the same conclusion as the North American study team:
“Lenalidomide plus dexamethasone is more effective than high-dose dexamethasone alone in relapsed or refractory multiple myeloma.”
President and co-founder of the International Myeloma Foundation, Susie Novis, said:
“Myeloma has been a difficult disease to cure, but with the novel therapies we are developing effective, long-term treatments by using multiple drugs in sequence and in various combinations. The addition of a drug with the potency of Revlimid to this equation is especially important.”
Revlimid has been approved for use in multiple myeloma in both Europe and the US, where it is also approved for treatment of a pre-leukemia condition called MDS. It is currently being tested for the treatment of other other leukemias, lymphomas and solid tumors.
Myeloma accounts for 16,000 new cases of cancer and 11,300 deaths every year in the US, where about 56,000 people are living with the disease. There is no cure but there are several treatments aimed at enhancing quality of life and survival.
“Lenalidomide plus Dexamethasone for Relapsed Multiple Myeloma in North America.”
Weber, Donna M; Chen, Christine; Niesvizky, Ruben; Wang, Michael; Belch, Andrew; Stadtmauer, Edward A; Siegel, David; Borrello, Ivan; Rajkumar, S Vincent; Chanan-Khan, Asher Alban; Lonial, Sagar; Yu, Zhinuan; Patin, John; Olesnyckyj, Marta; Zeldis, Jerome B; Knight, Robert D; the Multiple Myeloma (009) Study Investigators.
N Engl J Med 2007 357: 2133-2142
Volume 357:2133-2142,November 22, 2007, Number 21
“Lenalidomide plus Dexamethasone for Relapsed or Refractory Multiple Myeloma.”
Dimopoulos, Meletios; Spencer, Andrew; Attal, Michael; Prince, H Miles; Harousseau, Jean-Luc; Dmoszynska, Anna; Miguel, Jesus San; Hellmann, Andrzej; Facon, Thierry; Foa, Robin; Corso, Alessandro; Masliak, Zvenyslava; Olesnyckyj, Marta; Yu, Zhinuan; Patin, John; Zeldis, Jerome B; Knight, Robert D; the Multiple Myeloma (010) Study Investigators.
N Engl J Med 2007 357: 2123-2132.
Volume 357:2123-2132, November 22, 2007, Number 21.
Written by: Catharine Paddock