How does Pomalyst work?
Myeloma is a type of cancer that affects a specific type of immune cell called B-cells. The role of B-cells is to produce antibodies to fight infections from bacteria and viruses. Myeloma cells accumulate in the bone marrow and severely affect the production of other blood cells. This accumulation can also cause bone fragility and pain as well as kidney disease.
The active component in Pomalyst is pomalidomide, a small molecule that is structurally analogous to thalidomide (marketed as Thalomid), and lenalidomide (marketed as Revlimid), which are also used to treat myeloma. Currently, Revlimid is used as one of the main treatments for myeloma, when a patient is first diagnosed.
However, myeloma sometimes becomes resistant to Revlimid or does not respond to it. Research has shown that in such cases, Pomalyst can be effective.
- inhibiting the growth and survival of Revlimid-resistant myeloma cells.
- improving normal immune function, especially in immune cells called T-cells and natural killer cells which can effectively identify and kill malignant myeloma cells.
- suppressing the production of pro-inflammatory cytokines (cell-signaling molecules that promote inflammation), such as tumor necrosis factor-α and interleukin-6, which are required for myeloma cells to grow and spread.
- altering the bone marrow environment and making it non-conducive for myeloma cells to growth and survive.
Overall, Pomalyst in combination with other anti-cancer treatments such as dexamethasone (an anti-inflammatory steroid) and Velcade (bortezomib, a proteasome inhibitor) can improve progression-free survival in patients with myeloma who are no longer responding to primary treatment regimens or have relapsed or refractory myeloma. Progression-free survival is defined as the time from the start of a clinical trial to the first occurrence of disease progression or death.
Pomalyst in clinical trials
Several clinical trials have tested the safety, tolerability, and efficacy of different combination therapies that included Pomalyst and led to its approval. A few examples are summarized below.
A multicenter, open-label, randomized Phase 2 study (NCT00833833) assessed the safety and efficacy of Pomalyst (POM) with or without low-dose dexamethasone (LODEX) in patients with relapsed or refractory multiple myeloma. The patients had received at least two prior therapies (including Revlimid and Velcade), but the cancer had progressed within 60 days of their last therapy.
In the study, a total of 113 patients received POM+LODEX and 108 patients received POM alone. Patients received 4 mg a day of POM on days 1 to 21 on a 28-day cycle with or without 40 mg per week of LODEX. The patients were followed-up for a period of 14.2 months. The primary endpoint was progression-free survival.
The results were published in the journal Blood. The median progression-free survival for the POM+LODEX group was 4.2 months compared with 2.7 months for the POM group. POM+LODEX was found to be effective and well-tolerated.
Based on these results, in February 2013, the U.S. Food and Drug Administration (FDA) approved Pomalyst plus low-dose dexamethasone for patients with multiple myeloma who have received at least two prior therapies, including Revlimid and Velcade, and have demonstrated disease progression on or within 60 days of completion of the last therapy.
A multicentre, open-label, randomized Phase 3 trial (NCT01311687) was conducted in patients who were diagnosed with refractory, or relapsed and refractory multiple myeloma. These patients had failed at least two previous treatments with Revlimid and Velcade.
In this study, 302 patients received 28-day cycles of oral Pomalyst (4 mg per day on days 1 to 21) plus low-dose oral dexamethasone (40 mg per day on days 1, 8, 15, and 22) whereas 153 patients received 28-day cycles of oral Pomalyst (4 mg per day on days 1 to 21) plus high-dose oral dexamethasone (40 mg per day on days 1 to 4, 9 to 12, and 17 to 20). The primary endpoint was progression-free survival. The median follow-up was 10 months.
The results were published in The Lancet Oncology. The median progression-free survival for the Pomalyst plus low-dose dexamethasone group was substantially higher at 4 months compared with 1.9 months for the Pomalyst plus high-dose dexamethasone group.
The FDA approved Pomalyst plus low-dose dexamethasone in April 2015 for the treatment of patients with relapsed and/or refractory multiple myeloma who previously received at least two previous lines of therapy, including Revlimid and a proteasome inhibitor, and whose disease progressed during or within 60 days of completing the last therapy.
A randomized open-label Phase 2 trial (NCT02654132) assessed the efficacy of adding Empliciti (elotuzumab) to Pomalyst and low-dose dexamethasone compared to Pomalyst plus low-dose dexamethasone in relapsed or refractory multiple myeloma patients. Empliciti is a monoclonal antibody developed by Bristol Myers Squibb that helps natural killer cells to identify myeloma cells and kill them efficiently.
A total of 60 patients were randomly assigned to the Empliciti group (Empliciti plus Pomalyst plus low-dose dexamethasone) and 57 patients were assigned to the control group (Pomalyst plus low-dose dexamethasone).
The results that were published in the New England Journal of Medicine showed that after a minimum follow-up period of 9.1 months, the median progression-free for the Empliciti group was 10.3 months compared with 4.7 months in the control group. The overall response rate was 53% in the Empliciti group as compared with 26% in the control group. The overall survival rate is defined as the percentage of patients whose cancer cannot be detected following treatment.
Based on these data, the FDA approved Empliciti in combination with Pomalyst and dexamethasone in November 2018 for the treatment of adult patients with multiple myeloma who have received at least two prior therapies, including Revlimid and a proteasome inhibitor.
The side effects associated with the use of Pomalyst include life-threatening birth defects or death of an unborn child if the patient is pregnant. To avoid embryo-fetal exposure, the treatment is only available under a restricted program called Pomalyst REMS.
Other side effects include the risk of life-threatening blood clots that can cause deep vein thrombosis and pulmonary embolism, neutropenia (low counts of neutrophils, a type of immune cell), anemia (low counts of red blood cells), peripheral neuropathy (impairment of the nerves of the hands, arms, legs, and feet, causing tingling sensations or pain), and fatigue.
Pomalyst’s developer, Celgene, is expected to merge with Bristol-Myers Squibb by the end of 2019.
Last updated: Nov. 10, 2019
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