MRD test, The Next Big Thing in Multiple Myeloma--Dr. Brian Durie's Interview at China MM Summit Symposium 2015

Brian Durie, MD Professor
Cedars-Sinai Medical Center
Los Angeles, CA
Chairman, International Myeloma Foundation
Photo taken at China MM Summit Symposium,
May 15-18, 2015
Photos: Oncology Frontier(肿瘤瞭望)

Oncology Frontier《肿瘤瞭望》：Cytogenetics feature is important to Multiple Myeloma's Prognosis, is there treatment according to MM's classification?

Dr.Durie：The risk stratification of myeloma is very important in attempting to provide the best treatment options for each patient.

The problem is that even when we have some classification like mSMART (developed by the Mayo Clinic using cytogenetics and FISH to classify high- and low-risk)，the question remains which treatment we should use for high- and low-risk.

Currently, we really don't have a good treatment for high-risk patients.

In the clinical trials in the US in the Southwest Oncology Group (SWOG)，we classify high-risk using a few features -17P-，high-risk by gene expression profiling, high-risk based on high LDH or development of plasma cell leukemia or disease outside the bone marrow (extramedullary disease).

For these patients we use standard therapy VRD (velcade-bortezomib，revlimid-lenalidomide and dexamethasone) plus a new drug，alemtuzumab.

Or we have a new protocol, VRD plus daratumumab (an antibody against CD38).

We have new trials underway for the best treatment for high-risk myeloma but right now we don’t have a clear recommendation for individual patients coming into the clinic.

For now，one strategy that is practical is to diagnose high-risk based on patients who relapse early. Lesser-risk patients can stay in remission for two years or longer. High-risk patients will relapse after one or two years.

This is a very simple approach. For people with early relapse, we will introduce new drugs using multi-drug combinations. But this remains a major unmet need-how to treat high-risk versus low-risk patients?

China MM Summit Symposium, Beijing
Photo: Medlive.cn

Can you please comment on Minimal Residual Disease MRD test in multiple myeloma？

Dr.Durie：The IMF (International Myeloma Foundation) is very pleased to collaborate with several groups to develop the best MRD test.

The most successful collaboration has been with the Spanish team and we are very pleased at this meeting here in Beijing, Dr. Bruno Paiva from the Navarra University in Pamplona, Spain will discuss the use of next-generation flow for the assessment of MRD.

This is a method using a special cocktail of monoclonal antibodies to identify the amount of minimal residual disease in the bone marrow.

With this standardized cocktail, we can have a very accurate way to identify myeloma at the level of one-in-a-million (one myeloma cell in one million cells counted).

This is sufficient to identify patients who are having an extremely deep response and is a goal of the new approaches to treatment to achieve the maximum response and the maximum length of remission and survival.

There is a new overall goal with MRD-negative as the best treatment goal for patients with myeloma.

We are hopeful that the next-generation flow technique can be widely applied and will allow groups everywhere around the world to integrate this testing into their treatment protocols.

Dr. Durie presents award to Dr. Wenming Chen
Photos: Medlive.cn

Efficacy evaluation is crucial to multiple myeloma, what is the criteria used for complete remission？

Dr.Durie: The criteria for complete remission are very important because we want to be able to be precise when comparing one treatment with another.

Right now we need to have the best combinations so we use mostly triple therapies. Maybe the best one we have at the moment is Kyprolis (carfilzomib) with Lenalidomide and dexamethasone.

This achieves the highest level of complete remission. We can compare that to maybe just giving two drugs，Lenalidomide and dexamethasone alone.

The percentage that achieve a CR is obviously a lot higher with the three drugs versus two drugs. We need to have very precise definitions.

So the International Myeloma Working Group has established these criteria and DrShaji Kumar is working on new criteria to make the stringent CR even better for use in clinical trials everywhere.

Peripheral neuropathies is common complication in myeloma, how to manage it properly in clinical practice? 

Dr.Durie: Nerve damage can be caused by myeloma so there are patients in whom the myeloma protein damages the nerves to cause peripheral neuropathy.

This is seen as loss of sensation (numbness of hands and feet) and sometimes is painful with pain in the hands and feet or arms and legs. Treatment for that is rather difficult.

A key point is to diagnose early and avoid progression to severe neuropathy. Once there is nerve damage，it is difficult for the nerves to regenerate and recover well.

This is also an area of active research and many labs are working to enhance nerve regeneration. For now though，the only two possibilities are: to treat early to avoid the development of peripheral neuropathy; or using medication to counter pain like gabapentin.

If a patient has numbness， they need to be cautious of their activity to not cause damage to hands and feet because of the absence of pain or temperature sensation.

This is a challenging problem and we strongly recommend that there is education for neurology teams so they would be aware that neuropathy can be caused by early myeloma and referrals are made for consultation and treatment for the myeloma. These are the current strategies to achieve the best outcomes in these cases.

References：
　　
MM诊断和治疗中存在的问题——国际骨髓瘤基金会（IMF）主席Brian Durie教授访谈
2015/5/22 肿瘤瞭望  公众微信

2015年多发性骨髓瘤高峰论坛在京隆重召开 医脉通 May 19, 2015