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Goals of Therapy for Symptomatic Myeloma

Panelists: Keith Stewart, MB, CHB, Mayo Clinic; Gareth Morgan, MD, PhD, University of Arkansas for Medical Science; Saad Z. Usmani, MD, Levine Cancer Institute/Carolinas Healthcare System; Ivan M. Borrello, MD, Johns Hopkins Kimmel Cancer Center; Thomas G. Martin, MD, University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center; Sagar Lonial, MD, Winship Cancer Institute of Emory University
Published: Wednesday, Jun 21, 2017



Transcript:

Keith Stewart, MB, ChB:
Hello. Thank you for joining this OncLive Peer Exchange® on “Novel Concepts in the Management of Multiple Myeloma.” We continue to see dramatic shifts in the management of multiple myeloma. For newly diagnosed disease, we now have highly active regimens that achieve long-term remissions. In the relapsed/refractory setting, we have successfully improved outcomes by combining next-generation agents and monoclonal antibodies. As many patients are living with chronic myeloma, we are making efforts to better address long-term complications and improve quality of life. During this expert panel discussion, my colleagues and I will discuss the newest information available to help guide decision making in clinical practice.

I am Dr. Keith Stewart, the Vasek and Anna Maria Polak professor of cancer research at the Mayo Clinic in Scottsdale, Arizona. Joining me for this discussion are Dr. Ivan Borrello, associate professor of oncology at Johns Hopkins University School of Medicine and director of Cell Therapy Core at Johns Hopkins Kimmel Cancer Center in Baltimore, Maryland; Dr. Sagar Lonial, professor and chair in the Department of Hematology and Medical Oncology at Emory University School of Medicine and the chief medical officer of Winship Cancer Institute of Emory University in Atlanta, Georgia; Dr. Thomas Martin, clinical professor of medicine and associate director of the Myeloma Program at the University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center; Dr. Gareth Morgan, professor of medicine, director of the Myeloma Institute, and deputy director of the Winthrop P. Rockefeller Cancer Institute at the University of Arkansas for Medical Science in Little Rock, Arkansas; and Dr. Saad Usmani, chief of the Plasma Cell Disorders Program and clinical professor of medicine in the Department of Hematology, Oncology and Blood Disorders at Levine Cancer Institute/Carolinas Healthcare System in Charlotte, North Carolina. Thank you all for joining this discussion. Let’s begin.

We’re going to start off with a newly diagnosed patient, and we’re going to talk first about our goals of therapy today in 2017. I’m going to start with you, Gareth. You’re working at the University of Arkansas. There’s a reputation there for treating myeloma fairly aggressively. When you start treatment, what is the end game of your therapy?

Gareth Morgan, MD, PhD: I think things have changed in the last few years. It used to be sufficient to achieve a remission, but I think there is so much potential for residual disease to be left within that definition that people have started to use definitions of complete response that include MRD [minimal residual disease] status, by which I mean the level of residual disease.

Keith Stewart, MB, ChB: Your goal when you start therapy is to aim for a very deep remission right off the bat?

Gareth Morgan, MD, PhD: Yes, I think that is the aim of treatment in the modern world—to achieve MRD-negative complete remissions. You don’t have to achieve that in the first month, but it’s ultimately where you should aim to get all patients.

Keith Stewart, MB, ChB: Saad, would you agree with that? What’s your approach in the Carolinas?

Saad Z. Usmani, MD: I would agree with that for younger, more robust, transplant-eligible patients. But for elderly patients, I think you have to compromise a little bit on efficacy for the tolerability and safety. So yes, achievement of a deep response is important for those patients, but it may take a little longer than in the younger patients.

Keith Stewart, MB, ChB: Ivan, does it matter how fast you get a response? Does that matter anymore? Is slow better sometimes?

Ivan M. Borrello, MD: I think if there’s a patient who presents in extremis, in acute renal failure, then the rapidity of the reduction of the disease burden is important. But those, fortunately, occur in few patients. In the vast majority, not necessarily. What I’ve seen is that as long as the trend is going in the right direction, certainly, I think that allows us to deliver therapy with potentially less intensity and less toxicity that can be done over a longer period of time.

Keith Stewart, MB, ChB: Maybe I’ll just get the last 2 of our panelists to comment on this quickly. Tom, what is your approach in San Francisco?

Thomas G. Martin, MD: I agree with what my colleagues have said. We definitely try to treat patients to the deepest possible remission. We don’t try to do it in the first week or the first month, but certainly, our plan is over the first 3 to 6 months to try to achieve at least a CR [complete response]. And if we do get a CR, our plan is to try to assess for MRD negativity. In the older population, again, I agree with Saad that we really don’t push them too hard. I tell them, “You’re going to be on therapy for, potentially, upward of a year. Hopefully each month it will go down, slowly, slowly, slowly.”

Keith Stewart, MB, ChB: What is your frontline therapy of choice for both a younger and a more elderly patient? Sagar, I’d like to start with you.

Sagar Lonial, MD: For the transplant-eligible patient, our upfront regimen of choice is bortezomib with lenalidomide and dexamethasone. For the older, truly frail patient, because I think everybody else would be put in that category, it’s probably lenalidomide and dexamethasone. And now there may be talk about an antibody there.

Keith Stewart, MB, ChB: Gareth, I’m going to come to you last because I think you may be a little bit of an outlier. Ivan, what’s your upfront therapy?

Ivan M. Borrello, MD: I agree with Sagar. It’s a proteasome inhibitor, an IMiD [immunomodulatory imide drug], and for the most part, we’ve been using bortezomib and lenalidomide. We have not adopted carfilzomib as an upfront therapy, not to say that maybe that won’t change our decisions with new emerging data coming out. And if they’re truly frail, then a 2-drug regimen is probably a safer thing to do versus a 3-drug regimen. We have used 3 drugs in an elderly population, just less dose intensely.

Keith Stewart, MB, ChB: Are any of you using carfilzomib on a routine, regular basis, or still in clinical trials? Tom?

Thomas G. Martin, MD: In patients who are less than 50 years of age, we use carfilzomib, lenalidomide, and dexamethasone as our frontline therapy.

Keith Stewart, MB, ChB: Why 50? That’s a pretty young cutoff? Why not 55?

Thomas G. Martin, MD: That’s a good question. We see a fair amount of people who are less than age 50. I will also do it in patients between ages 50 and 60. At an age of less than 50, they don’t even bat an eyelash. They can take carfilzomib, lenalidomide, and dexamethasone to transplant and then more of that for upward of a year to 2 years and have no problem whatsoever, with the goal of achieving MRD negativity. In patients who have high-risk cytogenetics—say they have 17p deletion or t[4;14] deletion or 1q gain—I start right out of the gate with carfilzomib, lenalidomide, and dexamethasone.

Keith Stewart, MB, ChB: And Gareth, the last word goes to you on this point.

Gareth Morgan, MD, PhD: We try to customize the induction regimen to the patient. We still use combinations with some classic chemotherapy agents. And then we harvest stem cells and move on to some form of stem cell transplantation. But we are aiming each point in the process to achieve increasing remissions—aiming for MRD negativity ultimately.

Transcript Edited for Clarity

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Transcript:

Keith Stewart, MB, ChB:
Hello. Thank you for joining this OncLive Peer Exchange® on “Novel Concepts in the Management of Multiple Myeloma.” We continue to see dramatic shifts in the management of multiple myeloma. For newly diagnosed disease, we now have highly active regimens that achieve long-term remissions. In the relapsed/refractory setting, we have successfully improved outcomes by combining next-generation agents and monoclonal antibodies. As many patients are living with chronic myeloma, we are making efforts to better address long-term complications and improve quality of life. During this expert panel discussion, my colleagues and I will discuss the newest information available to help guide decision making in clinical practice.

I am Dr. Keith Stewart, the Vasek and Anna Maria Polak professor of cancer research at the Mayo Clinic in Scottsdale, Arizona. Joining me for this discussion are Dr. Ivan Borrello, associate professor of oncology at Johns Hopkins University School of Medicine and director of Cell Therapy Core at Johns Hopkins Kimmel Cancer Center in Baltimore, Maryland; Dr. Sagar Lonial, professor and chair in the Department of Hematology and Medical Oncology at Emory University School of Medicine and the chief medical officer of Winship Cancer Institute of Emory University in Atlanta, Georgia; Dr. Thomas Martin, clinical professor of medicine and associate director of the Myeloma Program at the University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center; Dr. Gareth Morgan, professor of medicine, director of the Myeloma Institute, and deputy director of the Winthrop P. Rockefeller Cancer Institute at the University of Arkansas for Medical Science in Little Rock, Arkansas; and Dr. Saad Usmani, chief of the Plasma Cell Disorders Program and clinical professor of medicine in the Department of Hematology, Oncology and Blood Disorders at Levine Cancer Institute/Carolinas Healthcare System in Charlotte, North Carolina. Thank you all for joining this discussion. Let’s begin.

We’re going to start off with a newly diagnosed patient, and we’re going to talk first about our goals of therapy today in 2017. I’m going to start with you, Gareth. You’re working at the University of Arkansas. There’s a reputation there for treating myeloma fairly aggressively. When you start treatment, what is the end game of your therapy?

Gareth Morgan, MD, PhD: I think things have changed in the last few years. It used to be sufficient to achieve a remission, but I think there is so much potential for residual disease to be left within that definition that people have started to use definitions of complete response that include MRD [minimal residual disease] status, by which I mean the level of residual disease.

Keith Stewart, MB, ChB: Your goal when you start therapy is to aim for a very deep remission right off the bat?

Gareth Morgan, MD, PhD: Yes, I think that is the aim of treatment in the modern world—to achieve MRD-negative complete remissions. You don’t have to achieve that in the first month, but it’s ultimately where you should aim to get all patients.

Keith Stewart, MB, ChB: Saad, would you agree with that? What’s your approach in the Carolinas?

Saad Z. Usmani, MD: I would agree with that for younger, more robust, transplant-eligible patients. But for elderly patients, I think you have to compromise a little bit on efficacy for the tolerability and safety. So yes, achievement of a deep response is important for those patients, but it may take a little longer than in the younger patients.

Keith Stewart, MB, ChB: Ivan, does it matter how fast you get a response? Does that matter anymore? Is slow better sometimes?

Ivan M. Borrello, MD: I think if there’s a patient who presents in extremis, in acute renal failure, then the rapidity of the reduction of the disease burden is important. But those, fortunately, occur in few patients. In the vast majority, not necessarily. What I’ve seen is that as long as the trend is going in the right direction, certainly, I think that allows us to deliver therapy with potentially less intensity and less toxicity that can be done over a longer period of time.

Keith Stewart, MB, ChB: Maybe I’ll just get the last 2 of our panelists to comment on this quickly. Tom, what is your approach in San Francisco?

Thomas G. Martin, MD: I agree with what my colleagues have said. We definitely try to treat patients to the deepest possible remission. We don’t try to do it in the first week or the first month, but certainly, our plan is over the first 3 to 6 months to try to achieve at least a CR [complete response]. And if we do get a CR, our plan is to try to assess for MRD negativity. In the older population, again, I agree with Saad that we really don’t push them too hard. I tell them, “You’re going to be on therapy for, potentially, upward of a year. Hopefully each month it will go down, slowly, slowly, slowly.”

Keith Stewart, MB, ChB: What is your frontline therapy of choice for both a younger and a more elderly patient? Sagar, I’d like to start with you.

Sagar Lonial, MD: For the transplant-eligible patient, our upfront regimen of choice is bortezomib with lenalidomide and dexamethasone. For the older, truly frail patient, because I think everybody else would be put in that category, it’s probably lenalidomide and dexamethasone. And now there may be talk about an antibody there.

Keith Stewart, MB, ChB: Gareth, I’m going to come to you last because I think you may be a little bit of an outlier. Ivan, what’s your upfront therapy?

Ivan M. Borrello, MD: I agree with Sagar. It’s a proteasome inhibitor, an IMiD [immunomodulatory imide drug], and for the most part, we’ve been using bortezomib and lenalidomide. We have not adopted carfilzomib as an upfront therapy, not to say that maybe that won’t change our decisions with new emerging data coming out. And if they’re truly frail, then a 2-drug regimen is probably a safer thing to do versus a 3-drug regimen. We have used 3 drugs in an elderly population, just less dose intensely.

Keith Stewart, MB, ChB: Are any of you using carfilzomib on a routine, regular basis, or still in clinical trials? Tom?

Thomas G. Martin, MD: In patients who are less than 50 years of age, we use carfilzomib, lenalidomide, and dexamethasone as our frontline therapy.

Keith Stewart, MB, ChB: Why 50? That’s a pretty young cutoff? Why not 55?

Thomas G. Martin, MD: That’s a good question. We see a fair amount of people who are less than age 50. I will also do it in patients between ages 50 and 60. At an age of less than 50, they don’t even bat an eyelash. They can take carfilzomib, lenalidomide, and dexamethasone to transplant and then more of that for upward of a year to 2 years and have no problem whatsoever, with the goal of achieving MRD negativity. In patients who have high-risk cytogenetics—say they have 17p deletion or t[4;14] deletion or 1q gain—I start right out of the gate with carfilzomib, lenalidomide, and dexamethasone.

Keith Stewart, MB, ChB: And Gareth, the last word goes to you on this point.

Gareth Morgan, MD, PhD: We try to customize the induction regimen to the patient. We still use combinations with some classic chemotherapy agents. And then we harvest stem cells and move on to some form of stem cell transplantation. But we are aiming each point in the process to achieve increasing remissions—aiming for MRD negativity ultimately.

Transcript Edited for Clarity
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