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Continuous Therapy in Multiple Myeloma

Discussant: Kenneth Anderson, MD, Dana-Farber 
Published: Thursday, Sep 03, 2015


A number of therapies are available in the treatment of multiple myeloma that can prolong both progression-free survival (PFS) and overall survival (OS), states Kenneth Anderson, MD. It is understood now that it is critical not only to achieve a response in multiple myeloma but also to employ maintenance therapy or continuous therapy to prolong PFS and OS. 

In the past, thalidomide was used as maintenance therapy and conferred benefit in terms of prolonging the response, explains Anderson, but even at low doses, thalidomide was associated with the development of neuropathy. Studies have shown that lenalidomide, an immunomodulatory drug, is not associated with neuropathy and confers a PFS and OS advantage in the post-transplant setting and in those who are not eligible for transplant. Lenalidomide is the most common maintenance therapy at the present time, says Anderson.

The modification of maintenance strategies depends on the risk level associated with the multiple myeloma, states Anderson. Standard risk multiple myeloma, defined by genetic testing, can be maintained with lenalidomide alone. However, for patients with high-risk multiple myeloma, such as 17p deletion, a proteasome inhibitor, such as bortezomib, should be incorporated into the maintenance strategy. The HOVON trial in the Netherlands demonstrated that bortezomib prolonged PFS and OS in as a post-transplant induction and maintenance therapy.
 
The proteasome inhibitor ixazomib offers the opportunity to incorporate proteasome inhibition through an oral formulation. A new drug application has been submitted for ixazomib in combination with lenalidomide and dexamethasone as a treatment for patients with relapsed and/or refractory multiple myeloma. In a phase II study, continuous treatment with ixazomib induced an objective response rate of 90%. 
 
In general, proteasome inhibitors are generally well tolerated, adds Anderson. Before administering any therapy, the risks and benefits should be weighed, particularly for maintenance therapy, which will be administered for a longer duration. 
 
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A number of therapies are available in the treatment of multiple myeloma that can prolong both progression-free survival (PFS) and overall survival (OS), states Kenneth Anderson, MD. It is understood now that it is critical not only to achieve a response in multiple myeloma but also to employ maintenance therapy or continuous therapy to prolong PFS and OS. 

In the past, thalidomide was used as maintenance therapy and conferred benefit in terms of prolonging the response, explains Anderson, but even at low doses, thalidomide was associated with the development of neuropathy. Studies have shown that lenalidomide, an immunomodulatory drug, is not associated with neuropathy and confers a PFS and OS advantage in the post-transplant setting and in those who are not eligible for transplant. Lenalidomide is the most common maintenance therapy at the present time, says Anderson.

The modification of maintenance strategies depends on the risk level associated with the multiple myeloma, states Anderson. Standard risk multiple myeloma, defined by genetic testing, can be maintained with lenalidomide alone. However, for patients with high-risk multiple myeloma, such as 17p deletion, a proteasome inhibitor, such as bortezomib, should be incorporated into the maintenance strategy. The HOVON trial in the Netherlands demonstrated that bortezomib prolonged PFS and OS in as a post-transplant induction and maintenance therapy.
 
The proteasome inhibitor ixazomib offers the opportunity to incorporate proteasome inhibition through an oral formulation. A new drug application has been submitted for ixazomib in combination with lenalidomide and dexamethasone as a treatment for patients with relapsed and/or refractory multiple myeloma. In a phase II study, continuous treatment with ixazomib induced an objective response rate of 90%. 
 
In general, proteasome inhibitors are generally well tolerated, adds Anderson. Before administering any therapy, the risks and benefits should be weighed, particularly for maintenance therapy, which will be administered for a longer duration. 
 
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