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| Kenneth C. Anderson, MD Professor Program Director, Jerome Lipper Multiple Myeloma Center LeBow Institute for Myeloma Therapeutics Dana-Farber Cancer Institute PHoto: Oncology Fontier |
Oncology Frontier(肿瘤瞭望): Can you share your opinion on the best treatment plan for relapsed or refractory multiple myeloma?
Dr Anderson: The best treatment for patients with relapsed or refractory myeloma really depends on what the patient has had previously.
The NCCN has several approved category 1 treatments for relapsed myeloma – lenalidomide and dexamethasone, bortezomib, bortezomib and pegylated liposomal doxorubicin and most recently pomalidomide with dexamethasone and carfilzomib, and within two weeks now, panobinostat, the HDAC inhibitor, and dexamethasone.
The treatment for relapsed myeloma, in other words, can have many options but it really depends on what the patient has had before.
If they have had immunomodulatory drugs such as lenalidomide, we would probably treat with a proteasome inhibitor.
Conversely, if they have had a proteasome inhibitor, we might substitute an immunomodulatory drug at the time of relapse.
If, on the other hand, first-generation lenalidomide or bortezomib was used initially, then we would move to pomalidomide and dexamethasone or carfilzomib, one of the second-generation relapse treatments.
The most important message of all is that we have treatments for relapsed myeloma now that have very high response rates and in some cases can have durability in terms of years. So patients can really appreciate a benefit in progression free and overall survival.
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| NCCN 20th Annual Meeting Hollywood, FL March 31-April 2 National Comprehensive Cancer Network (NCCN) Photo:Oncology Frontier |
What is the role of targeted therapy in providing durable responses against drug resistance from mutations in myeloma?
Dr Anderson: Targeted therapies in myeloma that are specifically targeting mutations are not very common.
In some diseases, melanoma for example, the BRAF mutation is very common and specific inhibitors such as vemurafenib can be used in malignant melanoma very commonly and can be very effective.
In multiple myeloma, we haven’t really a dominant mutation. The BRAF mutation I mentioned occurs in 4-8% of patients with myeloma. There is some early data now that inhibitors such as vemurafenib can work in that subset of patients.
Ongoing work will define further and further new targets and subsets of patients. Perhaps the most exciting development in myeloma though is in the immune treatments.
Monoclonal antibodies, immunomodulatory drugs and even some of the newer modalities, vaccines and checkpoint inhibitor therapies, PD-1 or PD-L1, in very early experiences are very active.
I mention these because the immune treatments seem to be active even across many subsets of patients with myeloma.
So on the one hand, we have efforts being made to divide the disease and treat it with targeted therapies; and on the other, we have this very exciting immune treatment development that I think will be able to treat broad populations of patients with this disease.
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| A Patient Advocate Booth at NCCN 2015 Photo：Oncology Frontier |
Can you outline the recent changes that have occurred in the NCCN Guidelines as they relate to the treatment of myeloma?
Dr. Anderson: The latest update of the NCCN Guidelines is probably the most exciting yet.
In terms of the initial management of the myeloma patient with newly diagnosed disease, there are more options than ever before.
The most recent addition is lenalidomide and dexamethasone given continuously until the time of relapse.
This is based on a randomized trial, the FIRST trial, where lenalidomide and dexamethasone given continuously extended the overall and progression free survival of non-transplant candidates.
This is very exciting and further supports using novel drugs like immunomodulatory drugs together, not only as induction but also as a continuous and maintenance strategy.
In terms of the latest iteration for relapsed disease, the new guidelines now include for the first time, panobinostat and dexamethasone with bortezomib.
Panobinostat is a histone deacetylase inhibitor and a new class of agent for treating relapsed myeloma.
It will be the first of a whole new generation of this class of agents which currently allows us to use panobinostat with bortezomib, but someday more selective histone deacetylase inhibitors will be used, not only with protease inhibitors, but probably with immunomodulatory drugs as well.
So the most important thing about the NCCN Guidelines is that they have established algorithms or opportunities for treatment options for patients at different stages of the disease.
Reference:
[NCCN 2015]NCCN多发性骨髓瘤指南专家组主席Anderson博士：复发性骨髓瘤最佳治疗 with Video 2015-03-15 Anderson 肿瘤瞭望
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