Peter Voorhees, MD: Why don’t we go on and move on to module 2, where we’ll be talking about transplant-ineligible, newly diagnosed patients with multiple myeloma. What would be the goal of therapy for you for these patients?

Reed Friend, MD: I think these frailer, transplant-ineligible patients really focus on quality of life. Their focus is not necessarily on length. Their first question is, “How good of a quality of life will I have?” And honestly, I think oftentimes treatment does provide improved quality of life. That would be their goal, I think.

Peter Voorhees, MD: Yeah, I would agree with that. Obviously quality of life is impacted by getting the disease under control, because the quality of life is suffering from the disease itself, but also trying to mitigate the adverse effects of treatment along the way. As far as treatment strategies, if you’ve got somebody in their late 70s, 80s, they’re frailer and you don’t think they’re a good stem cell transplant candidate, what regimens are you thinking about in that group of patients?

Amy Soni, MD: My go-to in that situation would be daratumumab, Revlimid, and dexamethasone. I’ve had several [patients who] have done really well with that. If it were someone really frail, you could try daratumumab alone potentially. But I’ve had a number of patients who are even pushing 80 and have done well with it.

Kwabena Osei-Boateng, MD: Yeah, I totally agree. I actually have an 89-year-old woman who has done well on that regimen.

Peter Voorhees, MD: There was interesting data out of [the American Society of Clinical Oncology meeting]. This was a poster presentation. It’s not a head-to-head comparison, but it was looking at those patients 65 years of age and older who were treated in the SWOG S0777 study [NCT00644228] and then the [phase 3] MAIA trial [NCT02252172]. S0777 was the phase 3 study out of SWOG that looked at [lenalidomide]-dex vs len-bortezomib-dex induction therapy, followed by len-dex indefinitely for transplant-ineligible and transplant-deferred patients with newly diagnosed myeloma. MAIA was len-dex with or without daratumumab in transplant-ineligible patients as well. But they focused on just those patients who are 65 years of age and older, just to do a more fair comparison between the 2 studies, and they matched on a number of different factors, including cytogenetic risk, stage, etc. Interestingly, what they found was that there was a [progression-free survival] advantage with dara-len-dex vs len-bortezomib-dex for that group of patients. Now, recognizing this is not a head-to-head comparison, this is not a randomized trial, but it is suggestive. What are your thoughts about that?

Reed Friend, MD: That was very interesting because in the SWOG study, it looked like there weren’t as many over 65 years old, compared with the MAIA study that had a predominance of patients who were over 65. Seeing how well tolerated [the treatment] and the almost comparable outcomes is very encouraging. I would favor more of a MAIA approach, although obviously you have other options upfront, such as RVd lite [lenalidomide-bortezomib-dexamethasone]. I don’t think we use it as often now that we see such great data and tolerability with MAIA, the Dara-Rd arm.

Peter Voorhees, MD: There are some who are very strong believers in the use of proteasome inhibitors for patients who have high-risk cytogenetic abnormalities. We talked about that in the maintenance setting just a short while ago. Would any of you use a lenalidomide, bortezomib, and dex over dara-len-dex for somebody who has a high-risk cytogenetic abnormality?

Kwabena Osei-Boateng, MD: Not necessarily. I think the MAIA trial looked at people with high risk, and it showed benefit across the board.

Peter Voorhees, MD: I would generally agree with that. Are any of you using 4-drug strategies at this point in the older, frailer patient population who’s not going to transplant?

Amy Soni, MD: I haven’t.

Reed Friend, MD: I have not. I love to say start low and go slow with our frailer patients.

Peter Voorhees, MD: The way that I look at this, if you’re truly transplant ineligible, there’s the potential that more drug could potentially create problems. There are 2 phase 3 studies that are ongoing. There’s the CEPHEUS trial [NCT03652064], which is looking at RVd with or without dara for transplant-ineligible patients, and then there’s the IMROZ study [NCT03319667], which is looking at the very same question, but with isatuximab instead of daratumumab. We’ll see what those studies show.

I do have a number of patients with newly diagnosed myeloma who defer transplant. They’re transplant eligible, but they defer their transplant. If they have high-risk disease, I will sometimes go off script and I will use a 4-drug strategy for that specific patient. But again, you know, these are patients who are truly transplant eligible. We need to await the phase 3 data before we start using 4-drug strategies in our frailer patients, especially those who just have standard-risk disease.

Kwabena Osei-Boateng, MD: In that case, you would be collecting stem cells.

Peter Voorhees, MD: Correct. We would be collecting them after several cycles, 12 to 18 weeks, 4-drug therapy. Then we would resume their treatment for a defined period of time and then go on to maintenance therapy.

Transcript is AI-generated and edited for clarity and readability.