Because multiple myeloma frequently remains asymptomatic until the disease is in the advanced stages, it can be difficult to diagnose and has limited treatment options, resulting in a five-year survival rate of only 50.7%. In this Q&A session from i3 Health's live meeting series, Evolving Treatment Paradigms in Multiple Myeloma and Implications for Shared Decision Making, Carol Ann Huff, MD, Medical Director for the Johns Hopkins Kimmel Cancer Center, discusses strategies to enhance the treatment of multiple myeloma. She shares her perspective on the use of regimens such as DCEP and CarCyDex, the management of myelomatous meningitis, and the ongoing development of drugs to improve outcomes in patients with this disease.
When do you use the heavy-duty treatments like DCEP (dexamethasone/cyclophosphamide/etoposide/cisplatin)?
Carol Ann Huff, MD: Different people have different perspectives on those regimens, but it's just not clear to me what we get from those other than hematologic toxicities. We've had those regimens for over 20 years, and where are the survival differences?
In my experience, DCEP is not a regimen people can stay on for any extended period of time. It may get an aggressive disease down for a couple of months, but you definitely need something more.
What is your experience with myelomatous meningitis?
Dr. Huff: Unfortunately, once you have leptomeningeal disease, none of the drugs work very well. We use them––we've prolonged survival by six to nine months with some of the intrathecal chemotherapies—but they don't work well. Now, there is some data suggesting that selinexor has central nervous system penetration. We've tried to talk about doing a trial evaluating that combination, but it hasn't gotten a lot of traction.
The other thing that we're seeing more and more is extramedullary disease. As patients are living longer and the cells no longer respect the bone marrow confines, that gets difficult to treat as well.
Do you have a particular regimen for someone who starts off with plasma cell leukemia?
Dr. Huff: I recently had a patient who came in with a white blood cell count of 95,000, which was truly plasma cell leukemia. We debated back and forth whether we would do DCEP. We gave the patient CarCyDex (carfilzomib/cyclophosphamide/dexamethasone), and within one week, the white blood cell count was 5,000 with a normal differential. The patient is in a complete remission, and we're working rapidly to get her to intensification therapy.
Do you ever give patients 1 to 2 g of cyclophosphamide without transplant support, or for example, melphalan 20 to 50 mg/m2?
Dr. Huff: I do give patients 1 to 1.5 g/m2 of cyclophosphamide at times if I need to do something quickly as a bridge to get me to some other therapy. I don't do it with stem cell support, and they do okay.
Historically, I have a patient who is a very long-term survivor who got 30 mg/m2 of melphalan for a few doses because there was nothing else 15 to 20 years ago. The patient is still in remission at this point in time. Do we do it now? No, but there is melflufen, a different melphalan preparation in development. There is also bendamustine. These agents are there, but it's just hard in the era of new agents to say based on an anecdote, "This patient did well, so we should do those sorts of things."
About Dr. Huff
Carol Ann Huff, MD, Medical Director for the Johns Hopkins Kimmel Cancer Center and Associate Professor of Oncology and Medicine at the Johns Hopkins University School of Medicine, is an expert in the treatment of multiple myeloma and amyloidosis. She has been the principal investigator of numerous clinical trials. Dr. Huff and her collaborators have identified a flow cytometric-based blood analysis that can be used to quantify the number of myeloma cancer stem cells and track their response to treatment. Dr. Huff has received multiple awards for clinical and teaching excellence, including the Kimmel Cancer Center's Director's Teaching Award in Oncology in both 2006 and 2012, and has authored numerous research publications and book chapters on multiple myeloma and bone marrow transplantation.
For More Information
Dr. Huff is the Chair of i3 Health's CME-approved visiting faculty meeting series, Evolving Treatment Paradigms in Multiple Myeloma and Implications for Shared Decision Making. Contact i3 Health to request a meeting if you are interested in hosting this free presentation at your institution.
Transcript edited for clarity. Any views expressed above are the speaker's own and do not necessarily reflect those of i3 Health.