Unmet Needs and Future Directions in the Management of Multiple Myeloma

EP: 1.Overview on Risk Stratification in Multiple Myeloma

EP: 2.Triplet Induction Therapy in Patients With Transplant-Eligible NDMM

EP: 3.Quadruplet Induction Therapy in Patients With Transplant-Eligible NDMM

EP: 4.Transplant-Eligible NDMM: Selecting Induction Therapy Based on Risk Status

EP: 5.What is the Role of Transplant in Treating Patients With NDMM?

EP: 6.Determining Transplant Ineligibility in Newly Diagnosed Multiple Myeloma

EP: 7.Curability, Maintenance Therapy, and Unmet Needs in Multiple Myeloma

EP: 8.Frontline Treatment Regimens in the Setting of Transplant-Ineligible NDMM

EP: 9.Optimizing Treatment Strategies in Relapsed/Refractory Multiple Myeloma

EP: 10.Relapsed/Refractory Multiple Myeloma: Managing Patients on Bispecific Therapy

EP: 11.Role of CAR T-cell Therapy in Patients With Relapsed/Refractory Multiple Myeloma

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EP: 12.Unmet Needs and Future Directions in the Management of Multiple Myeloma

Transcript:

Andrew P. Dalovisio, MD: I think we’re coming to the close of the first half of our session talking about transplant-ineligible, transplant-eligible, and relapse disease. I wanted to just get a broad perspective and thoughts on some unmet needs and future perspectives from each of you. I could start with Dr [Kelly] Pippin.

Kelly Pippin, MD: I think an unmet need is a lot of primary care [physicians] are not comfortable making the initial diagnosis for this. A good thing would be to define this early when people are a little younger, recognizing a globulin gap. A lot of times nurse practitioners or primary care doctors order a free light chain ratio, but do they know what that means and how do they interpret those results? Recognizing the signs and symptoms of early disease and being able to diagnose it before there’s a hip fracture, I always feel like preventive things are our friend. And I think getting folks to recognize the signs and symptoms of this in the primary care setting is one of the biggest things we could do to prevent some of the morbidity of the disease once renal failure happens, for example.

Andrew P. Dalovisio, MD: Sure. I think that’s a great point. And to that, there are 2 large screening trials going on right now. One is in Iceland called the iSTOP [MM] trial [NCT03327597], where they basically enrolled the entire country. They all go through 1 single health system. It’s 175,000 people, and over half the patients agreed to do it. So, we have this large population-based study of checking everyone for SPEPs [serum and protein electrophoresis] and light change. And we’re starting to get data from that study showing that screening may have some benefit, but also may have some harm. Telling somebody they have an MGUS [monoclonal gammopathy of uncertain significance] can also have harm. What I think is a little bit more of a discipline study is the PROMISE study [NCT03689595] done out of Harvard, where they’re actually studying the high-risk patient population. So, African American [individuals] and those with first-degree family relatives and screening those patients. Obviously, with these kinds of screening trials, you need to show an overall survival benefit. It’s going to take years or decades to get [these] data. But my take is screening these high-risk patient populations is probably a good idea [in order] to pick this up a little bit early.

Ryan P. Griffin, MD: I think another unmet need, and something we need to do a better job at is we need to be trying as hard as possible to give patients treatment-free options. I like the MASTER study [NCT03224507]. I think the utilization of MRD [minimal residual disease] testing and trying to get people off maintenance, because what is maintenance? Maintenance is you’re still taking chemotherapy. You’re taking probably 2 drugs if you’re [in the] GRIFFIN trial [NCT02874742]. I think it’s a disservice, almost, telling patients sometimes maintenance because it’s still chemotherapy. I think getting people to treatment-free periods is a huge need. And I think…it’s sometimes a hard sell for autologous stem cell transplantation for the community setting. But I think saying that this might be able to get you to that treatment-free period…is attractive. And I think that’s one thing we should be trying to do better with.

Andrew P. Dalovisio, MD: I completely agree. One of the things I think we tend to do, and I’m probably a bad offender of, is thinking, “Oh, it’s just Revlimid [lenalidomide].” But we forget Revlimid makes you feel crummy. I’ll have people [who] have been on Revlimid maintenance for 5 years, [and when] they finally stop, go, “Oh my God, I feel like myself again.” You forget that you’ve been doing that to them and they’re willing to take that because it’s keeping their cancer in remission. But I do agree with you. We tend to forget that these maintenance drugs tend to make people feel crummy. Some other studies came out at ASH [the American Society of Hematology Annual Meeting & Exposition] this year, looking [at] if patients were still MRD negative after a certain amount of time on Revlimid maintenance, 3 years, 4 years, could they stop without any chance to relapse? And there’s some suggestion that might be the case. Obviously, we need longer data, but I agree with you. I think MRD is really going to provide us the ability to maybe get patients off drugs, at least for long holidays if not forever, for those [who] are maybe actually functionally cured. But that’s a great thought. Let’s move on to Dr [Ernest] Quintin.

Ernest C. Quintin, MD: In my community practice, I always have that question of sustainability. You touched base on CAR T cells and all this treatment being $500,000 a year. Some of my patients are having problems getting to day 1, day 4, day 8, and day 11 of the Revlimid. So, nobody really wants to talk about money and where it’s coming from. But at the same time there’s a Louisiana senator [who] said, “When you’re poor and you’re sick, you’re still poor.” So, I think … [CROSSTALK]

Andrew P. Dalovisio, MD: Very true.

Ernest C. Quintin, MD: [CROSSTALK] … One of those unmet needs is the ability to even actually get some of these treatments to the people [who] need them.

Thomas Atkinson, MD: I think I would just sort of echo that. The cost of these drugs is exorbitant sometimes, and while we have made such progress in the treatment, the real economic cost is hard to shoulder for a lot of patients, and it’s easy to not think about the financial toxicity. But if you engage your patients in those discussions, it can be really gut-wrenching to hear the financial toxicity. And not just myeloma, of course, but Revlimid is just a major offender in terms of the financial toxicity.

Andrew P. Dalovisio, MD: Andremember…most of these patients are living longer than a decade now. So, they have to deal with this financial toxicity for 10 years plus.I have patients who are by no means very financially secure, and they’ll tell me, “I can’t pay 2 grand a month for Revlimid; that’s my savings.” So everyone gets affected by this, and certainly…treatment-free periods would be a nice thing to have for our patients. Maybe I can move on to you, Dr [Thomas] Atkinson, have you had any other thoughts on unmet needs or future perspectives?

Thomas Atkinson, MD: Oh, well, I guess I already used it.

Andrew P. Dalovisio, MD: I’ll give you that one. I think that’s fair. I think economic toxicity is certainly a real thing. Again, we tend to forget about it as physicians when we talk to our patients. I think from my end, I think a couple of areas of unmet needs are really the ultra–high-risk patients. So those 2 or greater than high-risk cytogenetic abnormalities. Those patients just do poorly. And when I get those patients at diagnosis, I have a very different conversation with them than I do with a standard-risk patient. I do have a terminal cancer diagnosis when I get these ultra–high-risk myeloma patients. I do the same thing with my plasma cell leukemia patients. So, we need to have better strategies for those. I think standardized MRD testing is going to be exciting as Ryan talked about with the MASTER trial, and figuring out that if patients are MRD negative for 5 years in a row, does that mean they’re cured, and they can come off the drug? I think figuring that out, and I think we will have answers on that in the next 5 to 10 years. I also think using CAR T and bispecifics earlier in therapy. There are trials now looking at patients getting induction transplant vs induction, CAR T, then maintenance. So, what we’re figuring out is, can these bispecifics be used earlier…in CAR T and in therapy to get better outcomes? Again, it just makes the myeloma literature more dizzying than it already is right now. But I think it’s an exciting time to be treating these diseases like this.

Well, I think we’re nearing the end of our time. I really enjoyed this session with you. Thanks for joining us. I’m sorry I couldn’t be there in person.

Ernest C. Quintin, MD: I don’t want to feel like I’m closing the group or anything but I just actually wanted to say thank you to Dr Andy Dalovisio. With myeloma being the way it is, with all these new drugs, really having an expert opinion, and having somebody you can actually talk to and bounce ideas off of, [who is] always coming in very well informed and open to conversation, I think that’s a huge thing to have. One of the best things that I probably decided to do was stick around this area so I’m able to talk to other oncologists and see what they’re doing. I really appreciate you. So, thank you.

Andrew P. Dalovisio, MD: That’s very nice. And as I said, it’s great having all of you as colleagues. You’re wonderful to work with.

Transcript edited for clarity.