Management of Multiple Myeloma - Episode 12

Case 3: Treatment for Relapsed Myeloma with 17p Deletion

September 25, 2018

EXPERT PERSPECTIVE VIRTUAL TUMOR BOARDAjai Chari, MD:I think that’s a good segue into the clinical discussion. Give me 1 answer for your preferred regimen for the del(17p) hybrids. Is there such an answer?

Nina Shah, MD:For a newly diagnosed patient or in the relapsed setting?

Ajai Chari, MD:For relapsed disease. We have a relapsed patient. Is there 1 right answer?

Nina Shah, MD:I don’t think so. In this case, I probably would have gone with carfilzomib/pomalidomide/dexamethasone—KPd—because that regimen includes drugs that the patient has not been exposed to. I don’t think any patient should go through 1 million lines of therapy and not have seen carfilzomib at some point.

Ajai Chari, MD:So, just to clarify, at the point of progression, you would go to KPd?

Nina Shah, MD:Probably. That would have been on my list—or a clinical trial, of course. That is always a right answer. But she hadn’t seen those 2 drugs, so I would consider that.

Ajai Chari, MD:Do you consider del(17p) in your decision making?

Nina Shah, MD:Yes and no. On the one hand, you have to be practical. You have to think of drugs that the patient hasn’t had. On the other hand, you have to consider why this evolution happened—whether it’s truly a new clone or a clonal expansion. One other possible explanation is that sometimes people have their marrows done at different places. This may lead to different techniques and different findings. But she’s presenting in a sort of high-risk or aggressive way, so I’d probably believe it. Whether it affects the decision is difficult. We really don’t know the true prognostic indication or prognostic significance of the high risk, in comparing the different salvage regimens. That’s really not been looked at—not prospectively, for sure.

Ajai Chari, MD:What’s your go-to regimen for a first relapse?

Nina Shah, MD:This is very interesting because she didn’t have Revlimid [lenalidomide] maintenance, so I think that was a fair answer. Either daratumumab/Rd [lenalidomide/dexamethasone] or KRd [carfilzomib/lenalidomide/dexamethasone] would have been a good option for her. That’s probably what I would have done—1 of those 2 options.

Ajai Chari, MD:If she had been on lenalidomide maintenance, Ola, what would you have done?

C. Ola Landgren, MD, PhD:If she had been on lenalidomide maintenance and presented the way the presentation demonstrates right now, I would agree with Nina. I would choose carfilzomib/pomalidomide/dexamethasone. I just want to add a few details to help explain why I would do that. We see that the monoclonal protein went from 0.6 g/dL to 1.7 g/dL in just 6 months. We also know that there is evidence of multiple lytic lesions by imaging. So, there was a rapid progression of the protein. There are new bone destructions. And then, with the bone marrow, we don’t know how many cells there are in the bone marrow, but we know that there is a new finding—del(17p)—in half of the detected cells. So, anything here, unfortunately, breathes a bit of an aggressive biology. For that reason, I would give a proteasome inhibitor. Carfilzomib is the more powerful of all of the ones that we have. Given that she has received, in your example now, Revlimid maintenance, I would pick pomalidomide.

Ajai Chari, MD:I agree with you. KPd is a good example. Interestingly, we just covered all of the phase III studies, of which KPd is not studied in any of them.

Nina Shah, MD:Correct.

Ajai Chari, MD:Do you practice evidence-based medicine? How important is it to have a phase III study? We’re all at academic medical centers, but what would you tell the community doctor? Do you need a phase III study? How do you deal with insurance reimbursement? How does this all matter?

Nina Shah, MD:That’s a really tough question, because there’s not going to be a trial of carfilzomib/pomalidomide/dexamethasone versus daratumumab/pomalidomide/dexamethasone. These things are not going to happen, and so we have to take our best guess. When it comes to large phase III studies—which have a definitive patient population—with these first 1 to 3 prior lines of therapy or newly diagnosed cases, you can really point to it. But, as you get far off in the disease, looking at how many more lines people have had, each patient becomes more individual. I think it’s hard to say that phase III data are the end-all and be-all of everything. Your patient is never going to be that average patient in that particular trial. So, I feel comfortable, based on phase II data, recommending things like carfilzomib/pomalidomide/dexamethasone and daratumumab/pomalidomide/dexamethasone. How do you feel?

C. Ola Landgren, MD, PhD:Well, I think it’s a reflection of the fact that the field is moving forward very fast. It takes a lot of time to generate phase III data. In oncology, including both solid tumors and hematologic malignancies, many of the drugs that are being prescribed are not backed up by phase III data. It happens every day, everywhere around the world. It happens all the time. If you look at myeloma—specifically, in the United States—90% to 95% of all patients diagnosed with myeloma are treated by a private practice doctor. Many times, I think the newly diagnosed patients, probably at first or second relapse, can be treated based on this data. After that, it gets more and more complicated. That’s why we use the NCCN [National Comprehensive Cancer Network] guideline recommendations. That’s also how we get reimbursement. Comprehensive cancer centers are not always using that because we have a lot of these patients. They are usually referred to us. So, I think that’s kind of how that works.

Ajai Chari, MD:Yes. I think this is a great discussion on the complexity of dealing with relapsed disease. This was a very high-risk patient who had a very early relapse and a very short remission. It was less than a year, probably reflecting this high clonal burden of del(17p). There probably is no single right answer, right? At the end of the day, treatment always depends on patient factors, disease factors, and, in particular, in the relapsed setting, prior therapy. I thank all of you for this very interesting discussion. We hope this was very helpful.

Transcript edited for clarity.