The Current Treatment Landscape for Relapsed/Refractory Multiple Myeloma: A Case-Based Approach

Rhonda Hewitt: Welcome to this virtual round table on relapse/refractory multiple myeloma. My name is Rhonda Hewitt, and I'm a nurse practitioner in the hematology division at Stanford Health Care in Palo Alto, California. Joining me today are my two colleagues, Kevin and Ann, who will now introduce themselves.

Kevin Brigle: Thank you, Rhonda. I am Kevin Brigle. I'm a nurse practitioner in the heme-malignancy clinic at Virginia Commonwealth University Massey Cancer Center.

Ann McNeill: My name is Ann McNeill. I'm a nurse practitioner in the myeloma division at the John Theurer Cancer Center in Hackensack, New Jersey.

Rhonda Hewitt: Thank you, Kevin and Ann. So today we will be discussing the treatment of a patient who has known cardiac disease with a carfilzomib-based regimen for his relapsed/refractory multiple myeloma. James is a 72-year-old male diagnosed with IgA lambda multiple myeloma associated with renal insufficiency and anemia. He was treated by a community oncologist, and his induction included lenalidomide, bortezomib, dexamethasone. He achieved a VGPR or a very good partial response, which is a 90% reduction in his tumor burden. And that was followed by lenalidomide and dexamethasone maintenance. So on his first relapse, James received daratumumab, pomalidomide, dexamethasone, and on a progression again, he was switched to ixazomib, cyclophosphamide, and dexamethasone.

In July of 2021, he was in floored relapse with renal insufficiency with a creatinine of 2.5, a calcium elevation 13.9, anemia with a hemoglobin of 9.1 and platelets 108, and his lambda serum free light chains were 2,291. And his SPEP showed a protein spike of two grams. He was lethargic and presented for his visit in a wheelchair. At that time, he was deemed not to be a chemotherapy candidate, also not a transplant candidate due to his comorbidities at the time of presentation. And looking through his plan, I think Kevin, you were treating him and notably missing ... You point out that he had not received carfilzomib. Do you want to comment on that?

Kevin Brigle: Yeah, that's correct. And as we get down to his past medical history, you'll see that he has pretty significant cardiac history. He's had a CABG in the past, hypertension, things like that. And so the community oncologist was a little wary about using carfilzomib. Now he did have a cardiologist that he saw on a regular basis, but still that kept him from getting the carfilzomib.

Rhonda Hewitt: Yeah. So as you mentioned, his past medical history was significant for cardiovascular disease, coronary artery disease. And he had had the CABG in the past. He also had hypertension, which you were aware can be a risk factor when receiving carfilzomib. He had chronic kidney disease, chronic diarrhea, diverticulitis, had had some squamous cell cancers in 2019, a history of prostate cancer in 2018. He also had some Grade 2 peripheral neuropathy; compression fractures in L1, T1; and I think the only other thing, he had had a CVA and a history of GERD as well. So James is a retired engineer. He's married with one daughter, and both his daughter and his wife are active in James’s care. He lives about 90 minutes from the clinic. He is a former smoker. He drinks one to two drinks of alcohol per week. And interestingly, he served in Vietnam and had prior exposure to Agent Orange. Any thoughts on that?

Ann McNeill: We know that certain toxic exposures increase the incidence of myeloma. So that’s pretty interesting that he did have that kind of history.

Rhonda Hewitt: And a known exposure too.

Ann McNeill: Yeah. Interesting.

Rhonda Hewitt: So as we mentioned, no exposure to carfilzomib due to his cardiac disease and his history and the treating oncologist was not comfortable utilizing that. So the treating oncologist did recommend selinexor, but he was not clear on how to best use it. So he was referred to an academic medical center where Kevin saw it. So Kevin, do you want to talk a little bit about his treatment plan?

Kevin Brigle: Yeah. And so there was a little discussion concerning what would be the best option for him. He did respond to bortezomib. But [inaudible] would be, we could potentially go back to that and use that in combination with selinexor; that is an approved regimen. But the peripheral neuropathy was Grade 2, and it was actually painful as well. And so he was on a couple of meds for that. And so I think using bortezomib was definitely out for him. And so we opted for the carfilzomib for that reason. And we did get a cardiac evaluation, an echocardiogram. And he had a lot of abnormalities, but nothing that was so significant says ECHO was 55%. And thinking about carfilzomib, certainly the cardiac toxicity is a dose dependent and also a dose dense dependent.

So the thought would be, well, let’s not go full dose and let’s go to once weekly instead of twice weekly. And that would give us at least very good efficacy and hopefully we wouldn’t have some cardiac issues as that as well. Now, we did opt to combine that with selinexor, that is not an FDA-approved regimen, but it is an NCCN-recommended regimen, at least in certain cases. And I think he certainly fits into that category then as well. So the problem with selinexor is he had chronic diarrhea, and this was not insignificant either. It was very significant diarrhea. And so that became an issue as well. As we know that can be one of the side effects of the selinexor as well.

Rhonda Hewitt: I think most listeners probably haven't had a lot of experience with selinexor because I think it's something that we utilize more at the academic institutions than maybe in the community setting. Do either of you have any pointers or clinical pearls you can share on how you manage patients who are on selinexor?

Ann McNeill: So, first of all, I just want to say something about James and your treatment of him, Kevin. I agree that the community oncologist may be a little more fearful of using carfilzomib in this kind of patient, but we would actually do the same thing that you did. We would never exclude him from getting carfilzomib with that cardiac history. Again, with proper monitoring and just a lot of the diagnostics and stuff like that, he can safely get carfilzomib. But as far as the selinexor, I think patient education is crucial. So we really need to explain to patients what the potential side effects are or regarding the GI side effects and to manage the nausea, the weight loss, the diarrhea, tell the patients to call us.

Sometimes we really don't have to tell them, they call us a lot anyway. But to really explain what they may experience, why they should report it to us, and what we can potentially do about it and what to have on hand at home for management. Even though this drug, selinexor is oral, we tend to see them. Even if they're not on a combination regimen with another subQ or IV treatment, we tend to see these patients a lot in the clinic initially in the first couple of cycles to see how they're doing from a GI perspective.

Rhonda Hewitt: Yeah. I think that's a great point. Whenever we start somebody on this, we tell them the first couple months, they're probably going to be a little bit tough and we need really close contact with you in order to keep you on this. But if we can keep you on it, usually we see a response in the myeloma. So if they know that there's the potential benefit of that, it's easier to stay on it and easier to stay on it if we're seeing them frequently. So James was started on the carfilzomib but as Kevin said, it was 36 mg/m². And they did it once weekly as opposed to the twice weekly dosing. So once weekly times 3 every 4 weeks, so a 28-day cycle. And that was combined with the selinexor 70 milligrams once weekly in combination with dexamethasone 20 milligrams.

And then for supportive care, he was started on denosumab for bone health as well. So that a monthly therapy issue where ... So the side effects for James were actually manageable for the most part. He definitely had some fatigue, diarrhea, and anorexia. But he had a rapid steady response. So no detectable monoclonal protein by SPEP at the 3-month mark, and his lambda light chains and creatinine normalized within 6 months. His hemoglobin also normalized in 9 months and the intensity of his therapy, it was able to be decreased at the 9-month mark. So his carfilzomib went to every other week dosing, and that really improved his quality of life and his ability to do the things that he enjoyed in his day-to-day life.

So when we think about James, one of the things that comes to mind is, okay, he’s had many lines of therapy. Before he came to Kevin, he had had many lines of therapy. So when you’re thinking about the next treatment, this really requires careful review of previous treatment and the previous toxicities as well. So with James, as Kevin said, he had chronic diarrhea, he had peripheral neuropathy that was painful. So when you’re thinking about options for him, you need to look at the big picture and look at the side effect profile of the medications that you’re going to give. A big hole in his treatment regimen to date had been that he had not received carfilzomib. All of us agree that his cardiac history would not preclude him from receiving carfilzomib, but he really would need to be followed closely. And we would need to be in communication with his cardiologist and do the appropriate cardiology workup preceding his therapy.

And then at any point in time, if on therapy his symptoms got worse or he developed new side effects, we would, of course, hold and work it up at that point in time. The selinexor, it does require, as Ann pointed out, a lot of patient education and supportive medications as well. This is a medication that when we put people on it, it's a good idea to give them loperamide or an antidiarrheal because this is the patient that when the diarrhea starts, you want them to take an antidiarrheal. You don't want them to wait and come in and get their C. diff done and all that kind of stuff. So James has a stable VGPR, and I really liked Kevin, your idea of ... You got him into a good disease control and then you're backing up on therapy in order for him to maintain his quality of life. I don't know if you want to talk a little bit about that and then maybe tell us what you have in mind for, what about his next relapse? What might be some of the things that you might think for him?

Kevin Brigle: Yeah. And one of the things that we weren't really able to get into control was the diarrhea. We never quite found a cause for that. And that actually preceded by many years the issue. And so I don't think selinexor either worsened or made that any better. The difficulty, maybe Ann you can comment on this as well, is the anorexia that's associated with selinexor and people just have a difficult time just wanting to eat. And so while this particular patient did not lose a lot of weight, he did not gain any. And when we went to every other week dosing, he began to have an appetite and gain weight again, which certainly improved his quality of life emotionally as well as physically. So that was a very big thing. And so I think when we were able to see that response and getting down to every other week, it was a huge thing for him and his family then as well.

And then to bring up your other point then too, what next? You can almost say that every therapy in myeloma is a bridging therapy because we have to get to what's next on these things. And so obviously what we would be thinking of now is something BCMA directed. And obviously we have an antibody drug conjugate we could use, there’s a clinical trial on a bispecific antibody as well. So that's an option for him down the line, but we're obviously thinking about that. And we talked about those things—if these things do relapse—because patients do want to know what's next as well.

Rhonda Hewitt: Yeah. I think that's really key in myeloma, and I'm guessing that at your institution, you follow that same thing. When we see a patient, we have them on a current therapy, but we always have the next line of therapy, at next relapse, we would do this. Or maybe there might be a couple of options depending on how that relapse presents, but that's usually well documented in our charts so that if that relapse happens when the primary hematologist is out of town, everybody knows what's being discussed and what we should do at that point in time.

Ann McNeill: So just to comment on that, Rhonda, we know in our patients that for every relapse and subsequent remission, the duration of that response is shorter. So every time a patient who has multiple lines of therapy responds to a treatment, we're very cautiously optimistic on the length of disease control. So like Kevin and you both said, we're always thinking what's the potential next line of therapy? So we always have that in the back of our mind and the patients ask because they know. So clinical trials, like Kevin mentioned are a big thing in the major academic institutions. So definitely something that we are thinking about with every line of therapy.

Rhonda Hewitt: Great. Well, I think that brings us to the end of this case discussion. Please see the other segments for further discussion on relapse/refractory multiple myeloma, or visit advancedpractitioner.com.