Improving Outcomes in Newly Diagnosed Multiple Myeloma - Episode 7

Tailored Treatment Decisions for Transplant-Ineligible Multiple Myeloma

, , ,

Various considerations affect choice of first-line therapy for a patient with newly diagnosed multiple myeloma who is ineligible for transplant.

Saad Z. Usmani, MD: Next question is for Dr Korde. When you’re thinking about front-line treatment for transplant-ineligible patients, what’s going through your mind? How are you thinking about the treatment options? You don’t have head-to-head comparison between VRd [bortezomib (Velcade), lenalidomide (Revlimid), dexamethasone] and DARA/Rd [daratumumab (Darzalex) plus lenalidomide and dexamethasone]. What kind of things are you thinking about? This is an open question, so you guys can jump in.

Neha Korde, MD: Yeah. I’m looking at whoever is sitting in front of me. For that transplant-ineligible group, looking at the recently updated MAIA data, I feel that this regimen is the standard of care, at this point, in this group. I know that it’s hard to compare the 2 head-to-head, but when you look at the DRd [daratumumab, lenalidomide, dexamethasone]—the tolerability, how easy it is to give, and the lack of neuropathy—I think that tends to come to the forefront of my mind.

I’m also thinking about who the patient is. As you’re going through the different transplant-ineligible categories, for the person sitting in front of you, there can be a whole range of frailty and comorbidities. Look at the support system; who are the providers helping the patient? What I usually find, in my experience, is that the DRd tends to go very smoothly into those patients. It seems to work with few side effects and not a lot of neuropathies. I tend to prefer that, at this point, over RVd [lenalidomide, bortezomib, dexamethasone].

Saad Z. Usmani, MD: What do you guys think?

Sham Mailankody, MD: I agree.

Urvi Shah, MD: I completely agree with Neha. I tend to prefer DRd as well. I often, if the patient is extremely frail, will start with either a month of DARA [daratumumab] alone or Revlimid alone, and then add the drug with the second month.

Saad Z. Usmani, MD: Would you think about reducing the dose of lenalidomide to start off with or do you start with the higher dose and then reduce it?

Urvi Shah, MD: No, I start with the reduced dose. I start at around 15 mg usually, but it also depends on renal function, so it could be 10 mg or 15 mg. Sometimes could be 5 mg but that’s rare.

Saad Z. Usmani, MD: Sham, what do you think?

Sham Mailankody, MD: The data would suggest that as long as we don’t have randomized comparison data, any differences between 2 triplets is likely going to be somewhat marginal. I’ll come back to this, but I think there are very few patients who should be getting doublets with newly diagnosed myeloma in 2021. I think for most people, transplant eligible or ineligible, you will be able to do a triplet for the most part, but as Urvi said, starting with a doublet, adding a third dose reduced drug, starting with reduced doses of these different drugs, having less steroids, and less lenalidomide to begin with.

The fact that we have Velcade, we have daratumumab, and ixazomib [Ninlaro], among other drugs provides us these options to tailor treatments based on patient preferences. Like Urvi’s patient who doesn’t want to come in weekly, you have a choice. Your patient with diabetes and doesn’t want to get more neuropathy, you have a choice: daratumumab. Your patient who doesn’t want to sit 6 to 8 hours for their first infusion—although now it’s only the first infusion—he/she may choose 1 of the other choices. I think it’s very few. I won’t say no to patients, but certainly there are some patients who would benefit from a doublet because of comorbidities.

I think we should ask ourselves hard questions when we see these patients. Do I start this patient with a triplet from the get-go? Do I start with doublet and add something? If you start a patient with a low dose of lenalidomide, for instance, who is doing very well, then you could potentially go up in dosage if necessary. So what you start with does not necessarily need to be all of the 4 to 8 cycles, but keeping in mind what doses you started, how the patient is tolerating the treatment, and how they’re responding are good benchmarks when determining how to adjust—both go up on doses or go down—that would be helpful. But, again, I would make a big plug for more drugs, at least within reasonable limits, for patients with newly diagnosed myeloma.

Saad Z. Usmani, MD: I think this is the transplant-ineligible population that Neha alluded to this, that’s heterogeneous, too, right?

Sham Mailankody, MD: Correct.

Saad Z. Usmani, MD: So you’ve got your frail vs intermediate fit vs really fit patients. This is where, I think, what we probably need to do better in all of our practices. We need to engage with the geriatric oncology colleagues and actually have a formal geriatric evaluation for these patients to give us a “better than the eyeball test” of what to do for these patients. That’s something that we have to consider.

Sham Mailankody, MD: Trials have done a good job of quantifying and being objective about frailty. I guess it would be nice if we could be more objective with our assessment.

Neha Korde, MD: Yeah. There’s real-world data vs clinical trial data. They do a very good job assessing the geriatric population in the trials.

Saad Z. Usmani, MD: Feel free to share your experience. In my older patients with DRd, my expectation isn’t like the proteasome inhibitor [PI]-IMiD [immunomodulatory drugs]-steroid combination. You see a fairly drastic drop in a response fairly quickly within the first 2 or 3 cycles. With a monoclonal antibody-IMiD combination, especially in older patients where you’re dose attenuating regimens, you see ongoing responses for many months. So it’s not that you’re getting your best bang for your buck in the first few months. It’s like you have patients who go on to get that deepening of response for like 12 months, 14 months, or 18 months. I also find it interesting and appealing, from a therapeutic standpoint, that you can use that drug for a long duration of time and see that kind of therapeutic response.

Neha Korde, MD: Do you end up switching your patients to Revlimid alone after maintenance?

Saad Z. Usmani, MD: I wait for patients to get to a response plateau, and it also depends on how well they’ve tolerated it. If they have any count issues, my typical preference is to wean off the lenalidomide and keep the daratumumab once a month. Yes, it used to be more cumbersome when it was an infusion, but now it’s subcutaneous so, yes, they do have to come in. When they come in for labs, you can take care of the subcutaneous injection. There are other patients, if they’re standard risk and they’ve tolerated lenalidomide fine, you can wean off the daratumumab. That’s real-world practice. There are patients who are going to come to you and say, “Hey, I don’t want to disturb anything. I’m in a good response and I’m tolerating it fine. Don’t change anything.” And then you just go along with that plan. I think this is where it’s more clinical acumen and your patient preference.

Sham Mailankody, MD: The art of medicine.

Saad Z. Usmani, MD: The art of medicine, yeah. It has nothing to do with the clinical trial data.

Transcript edited for clarity.