Treatment considerations for relapsing multiple myeloma is discussed by key opinion leaders.
Jeffrey Matous, MD: One of the issues that I have as a physician is we’ve always defined relapsed/refractory myeloma based on the number of lines of therapy. I’m not sure that’s correct anymore.
Beth Faiman, PhD, APN-BC, CM: Nope. Not anymore.
Jeffrey Matous, MD: I think right now we have to think about triple-class exposed, penta-class exposed, triple-class refractory, and penta-class refractory. An issue we’ll run into is going to be with insurance payers and with FDA labels. We’re going to dive into that a little bit later. That’s usually what we do. Then always the caveat, we’re always looking for studies for patients as well.
Zahra Mahmoudjafari, PharmD, MBA, BCOP, FHOPA: Absolutely. Appreciate that.
Jeffrey Matous, MD: Kirollos, anything that we didn’t address?
Kirollos Hanna, PharmD, BCPS, BCOP, FACCC: No. I think everybody hit the nail on the head. I think just like you guys said, if we have incorporated CD38 in the front, we’re going to see that in that second-line setting. That’s 99% of the time. If you didn’t incorporate the CD38, you’re going to switch your PI [proteasome inhibitors] and your IMiDs [Immunomodulatory imide drugs]. Again, your Kyprolis [carfilzomib] is going to be your next potential option with pomalidomide [Pomalyst] or maybe lenalidomide [Revlimid] depending on how your provider dictated that patient to be, whether it’s lenalidomide refractory or not.
I think to Beth’s point about the selinexor [Xpovio]-dosing. What we learned from DLBCL [diffuse large B cell lymphoma] and how we can’t change the dose of selinexor. Nobody can tolerate that twice-a-week dosing regardless of high-dose dexamethasone trying to serve as an anti-emetic, plus being an anti-myeloma treatment. The supportive care there is critical. Then, as you said, the third line, we still can do one of these triplets and just maneuver things around a little bit. I was really excited about belantamab [Blenrep]. I love ADC [antibody-drug conjugate] technology, just everything behind it. That DREAMM study didn’t pan out to be the confirmatory study we hoped it to be. But I do have a feeling in the future belantamab is coming back.
Jeffrey Matous, MD: Another myelotory?
Kirollos Hanna, PharmD, BCPS, BCOP, FACCC: Right.
Beth Faiman, PhD, APN-BC, CM: That’s exactly what I just said.
Kirollos Hanna, PharmD, BCPS, BCOP, FACCC: I do think it’ll come back hopefully without being as restrictive of a REMS [Risk Evaluation and Mitigation Strategy] program or as tedious of a REMS program. We have a lot of ADCs around these ocular toxicities. But now again, this BCMA [B-cell maturation antigen]-specific class. Now we can target it from so many different areas. We have good options and, as we know, the trajectory of what we’re going to see in myeloma, your BCMA is going to move to the third line. They’re going to move to the second line.
Beth Faiman, PhD, APN-BC, CM: Well, with the Ide-cel [idecabtagene vicleucel] therapy used in the KarMMa-3 study.
Kirollos Hanna, PharmD, BCPS, BCOP, FACCC: The KarMMa-3 study. Exactly. You brought up a really great point.
Jeffrey Matous, MD: Maybe class exposed as opposed to lines of therapy.
Kirollos Hanna, PharmD, BCPS, BCOP, FACCC: The class exposed. Exactly. You brought up a really good point around these labels. They tell you 4 prior lines or 4 prior therapies. I think the NCCN [National Comprehensive Cancer Network] has even started to help us a little bit more. The charts back in the day, as Zahra mentioned, I called it the kitchen sink. You could just bring this chart, and throw a dart at it, whatever it landed on was likely a category 1, category 2A.
Beth Faiman, PhD, APN-BC, CM: For reimbursement purposes.
Kirollos Hanna, PharmD, BCPS, BCOP, FACCC: Exactly. But now the NCCN further started to subdivide what the patient has progressed on and what are potential good regimens, which gives us some direction. Still a lot of ambiguity I think in the grand scheme of things. But that’s where I think from a managed care perspective as well, pathways, value drivers like health-related quality of life, potential cost, especially when you get into 3, 4 lines in. What’s a 40% response rate vs a 44% response rate? But a million-dollar price tag vs a $500,000 price tag? I think these are all very important conversations that we always have to have in myeloma, particularly that late into it.
Zahra Mahmoudjafari, PharmD, MBA, BCOP, FHOPA: It’s a really exciting time though in multiple myeloma. I’m sitting here thinking, I don’t know, 7, 8 years ago, none of these things were an option. I think I read somewhere recently that the median overall survival passed 3 or 4 lines of multiple myeloma therapy is 8 months. We’re seeing some significant improvements in progression-free survival in these trials. So these are unprecedented, and I really don’t love that word. I can’t believe I said that. But unprecedented numbers that we’re seeing in multiple myeloma in these treatments. It’s awesome. It’s very exciting. I can talk about costs all day long, but I think we’re not seeing these results anywhere else. It’s a really great time.
Jeffrey Matous, MD: Can I ask our panelists if they’re seeing any doublet therapy in the relapsed/refractory setting?
Beth Faiman, PhD, APN-BC, CM: Well, I don’t see very many doublet therapies here. I will ask though the one caveat is if you have a patient with a translocation 11;14, when do you pull the plug and offer venetoclax [Venclexta]? The BELLINI study found that such a benefit in the translocation 11;14 population in combination with bortezomib [Velcade] is safe. We have clinical trials with BCL2 [B-cell lymphoma 2] inhibitors. I think it’s an exciting class of drugs, but up to 26% of people will have that characteristic of FISH [fluorescence in situ hybridization]. When do you treat using that drug?
Jeffrey Matous, MD: The answer is yes. I have colleagues that do what I do at other places who really believe that for the 11;14s that venetoclax or BCL2 inhibitors should be employed early enough. I think that’s completely unknown, but it’s great to have that option and it’s great to think about that option. If you have a patient where you’re scratching your head, you’re looking at their prior regimens, and you’re going, what am I going to do for this patient next? You realize, aha, wait a minute. They had an 11;14 and so that’s a great point.
Beth Faiman, PhD, APN-BC, CM: It’s not an acquired translocation, but what I’m seeing is at the outside hospitals, they’ll be seen for an anemia consult. They’ll get a bone marrow biopsy, they won’t have FISH, or it’ll be so old they won’t be looking for translocation 11;14, or they’re not doing plasma cell enrichment. You didn’t have that characteristic identified. So we are repeating bone marrows to see if they have an 11;14, especially if they’ve had a bunch of prior lines of therapy.
Jeffrey Matous, MD: What are the challenges for patients with relapsed/refractory myeloma? You touched on some of them, Beth, in terms of bone health, infectious disease prevention, and thrombosis prevention. But what are other challenges that these patients have when they have relapsed/refractory disease that might be a barrier to their next line of therapy?
Zahra Mahmoudjafari, PharmD, MBA, BCOP, FHOPA: Gosh, there are so many. You did such a great job of touching all the points that I was going to discuss.
Beth Faiman, PhD, APN-BC, CM: I’m sorry.
Zahra Mahmoudjafari, PharmD, MBA, BCOP, FHOPA: No. It’s great. I think expanding beyond that and perhaps more focused on the quality of life. I think, again, these patients are significantly more and more deconditioned with every single line that they receive, and there are a lot of costs associated with this, just health care, utilization time, chair time. They really struggle, so it depends on just how resistant their disease is in terms of the manifestations of their disease. But in general, I like to focus a lot on the health care quality of life because that significantly impacted these patients. They really have a very challenging time the further along they progress.
Beth Faiman, PhD, APN-BC, CM: The physical, financial, and psychosocial issues are huge. That’s again why we try to underscore the importance of survivorship at diagnosis. Have somebody appointed that can walk them through, get them linked in with social workers, and dietary nutrition. We have financial counselors and the importance of support groups, the International Myeloma Foundation, the MMRF [Multiple Myeloma Research Foundation], there are lots of virtual support groups that empower the patients to take hold of their health. I might not see their kappa free light chain numbers before they do, and then they can help me follow their care a little bit better.
Jeffrey Matous, MD: What about the role of educating your patients? Pharmacists do a lot of educating patients and it’s so important, I think, in myeloma. Kirollos?
Kirollos Hanna, PharmD, BCPS, BCOP, FACCC: Myeloma treatment. That’s definitely one of the challenges. I think when I mentioned that you see all of the oncology within myeloma, you also see the complexity of it all. You have these triplet drug regimens for drug regimens, all with different schedules. So what are you doing in terms of education around their oral chemotherapy, around their dexamethasone dosing, which honestly don't get me started around dexamethasone dosing, especially around daratumumab [Darzalex] and how you should give it and what days you should give it. But it is very complex.
When you first approach a patient who’s newly diagnosed with myeloma or they’re now switching to a new regimen, oftentimes they are so overwhelmed with the amount of information. We try to develop for them a treatment calendar, 2 cycles in that treatment calendar is no longer relevant because either their IMiD is off schedule, their PI [proteasome inhibitor] is off schedule, their dexamethasone is off schedule and it’s extremely challenging. But then on top of that, you’re telling them to take aspirin every day or maybe therapeutic anticoagulation. On top of that, you’re telling them to remember to take their acyclovir twice a day. Then they’re coming in for their bisphosphonates or whatever they’re doing. They may be getting ESA [erythropoietin stimulating agents] so there are so many challenges from an educational perspective and I don’t really think we have a solid tool.
Another area though, where I think patients face challenges, which may be not something that patients seek out, but it’s certainly an unmet need, is enrollment in clinical trials. When you look at the clinical trials, a lot of times the demographics and characteristics of the patients doesn’t even reflect our myeloma population. You look at the African American patient population, look at the MajesTEC trial with teclistamab [Tecvayli]. Five percent of patients were African American. That’s not reflective of the myeloma patient population by any means. So that’s also, I think, a challenge into this entirety of this disease for the patients as well as for us as HCPs [health care providers] as well.
Beth Faiman, PhD, APN-BC, CM: I think there’s a clinician bias and there’s a lot of biases in health care, but how many times did we go into a room and say they’re not going to want a clinical trial because they live an hour and a half away? I offer everybody a clinical trial. I’ve had people drive back and forth, and a lot of the insurance companies will arrange transportation for them like the Medicaid-type companies. We know that African Americans are underrepresented as the biggest demographic. I just talked about the translocation 11;14. African Americans do better than their white counterparts if they’re offered the same treatments. So again, being aware of the implicit and explicit biases and offering everybody a clinical trial, I think is the wave of the future.
There’s the elranatamab study that’s open at my institution [Cleveland Clinic], and the only arm that’s still open is the African American arm so I think that the drug companies, the insurance payers are aware of this and they’re trying to really force us as clinicians to enroll these patients.
Transcript edited for clarity.