A latest research published in the New England Journal of Medicine (NEJM) on April 28, 2016, states that the inclusion of Ixazomib to the current treatment regimen can prolong the progression free survival of myeloma patients. This conclusion was based on the results of the phase 3 clinical trials funded by Millennium Pharmaceuticals.
The authors further state that the drug ixazomib can be added to the lenalidomide-dexamethasone oral treatment program. This lenalidomide-dexamethasone regimen is approved by FDA and is currently in use to treat multiple myeloma. Moreover, the toxic effects observed after the inclusion of this drug were also limited.
To attain the overall objective of progression free survival, a clinical study involving 722 patients was designed. The patients for this study were selected randomly. All of them were suffering from either refractory or relapsed or both types of multiple myeloma, a type of cancerous disease of bone marrow and plasma cells. Receiving lenalidomide-dexamethasone as an oral therapeutic regimen was in common. These patients were divided into two groups randomly and were subjected to double blinded, placebo controlled, phase 3 clinical trials. For the first group, ixazomib was added to the regimen and was named as ixazomib group while the second group was treated with placebo lenalidomide-dexamethasone and was named as placebo group.
In the study an increase in the progression free survival by six months was observed in the ixazomib group as compared to the placebo group. An increase in the overall response rate i.e., 78% for ixazomib group as compared to 72% for placebo group was also noted. Similarly, the objective response rate i.e., combination of complete and very good partial response rates was observed to be in the ratio of 48% to 39% for both groups, respectively. A decrease in death rate associated with the disease progression in the ixazomib group was also observed. The ixazomib group took median time of 1.1 months to respond as compared to 1.9 months for the placebo group. The total median duration of the response for both the therapies was 20.5 months and 15.0 month respectively. A median follow-up of the trials was conducted for about 23 months. After that time it was observed that there was no significant change in overall survival in both groups. The follow-up for this study is still ongoing.
The superiority of the study lies in the fact that it emphasized on the monitoring of some serious adverse and toxic drug events. No significant difference was observed in both test cases. The rate of life threatening adverse events were 2% lesser than placebo study group. The death rates during the therapy for both the groups were 4% and 6% respectively. Severe adverse effects of grade 3 for the two patient sub-groups were observed to be 74% vs 69% respectively. Thrombocytopenia having grade 3 and grade 4 severity occurred more commonly in ixazomib group with rate of 12% and 7% respectively versus placebo group having grade 3 and grade 4 severity with the rate of 5% and 4% respectively. The GI problems that were observed in both the groups were of less severity. The development of skin rashes in ixozamib group patients was 13% higher to placebo group patients. The chances of the development of peripheral neuropathy in ixozamib group and in the placebo group was similar i.e., 27%.
Although the results of the study are not making a significant difference but still due to the limited availability of other treatment options for multiple myeloma, FDA approved the ixazomib addition to the current regimen i.e., lenalidomide plus dexamethasone on the basis of the stats that the ixazomib group had survived for a longer period of time without worsening their diseased state as compared to the placebo group. It was observed that the ixazomib group survived for 20.6 months on average without worsening their condition in comparison to 14.7 months with the placebo group.
This drug is the patent of Millennium Pharmaceuticals, a subsidiary of Takeda Pharmaceuticals, USA and Japan, and hence the clinical trials were sponsored by the company itself and by observing the results of those trials FDA approved the drug and its addition to the existing drug therapy.
The drug ixazomib on the basis of clinical trials is now added to the previous oral treatment regimen involving two drugs lenalidomide plus dexamethasone and is now approved by FDA for treating the patients with multiple myeloma. On the basis of the results, the therapy can also be used in those patients who did not respond to the previous therapy.
The myeloma or multiple myeloma is the third most common type of the blood cancer in the United States after lymphoma and leukemia, according to the National Cancer Institute. It constituted almost 1.4% of the new cancer cases reported in 2014. Since 1975, an annual increase of 1% was observed in the US. It was estimated that there would be greater than 24,000 new registered cases of myeloma in 2014, out of which 11,000 would die. Similarly, in 2016, 30,330 new cases of myeloma are expected to be reported out of which 12,650 would probably die. The risk factors for the disease majorly include exposure to chemicals, radiations and chances of mutations due to aging.
About The Drug Ixazomib
Ixazomib (Ninlaro) is manufactured by Millennium Pharmaceuticals and was approved on May 20, 2015, by the US FDA. This drug can be used in combination therapy of the patients suffering from multiple myeloma. It acts through the blockage of the enzymes in the cells of multiple myeloma and is classified in the class known as proteasome inhibitor. As a result, the growth and division of myeloma cells is inhibited, stopping the disease progression. This drug is administered orally and can be added to another FDA approved treatment regimen i.e., dexamethasone and lenalidomide. Dexamethasone is a type of corticosteroid whereas lenalidomide (Revlimid) is an immunomodulatory agent. This drug is also used for treating multiple myeloma. It acts by killing the abnormal cells found in bone marrow. As a result the bone marrow cells produce normal blood cells.
“As we learn more about the underlying biology of multiple myeloma, we are encouraged to see the development of new ways to treat this disease,” said Richard Pazdur, MD, Director of the Office of Hematology and Oncology Products in FDA’s Center for Drug Evaluation and Research. He further said that this is the third drug approved by FDA for multiple myeloma this year after panobinostat (Farydak) and daratumumab (Darzalex) and provides the patients with a new form of oral treatment by which the progression of disease is slowed down, especially when other therapies have failed.