Recent Advances in Multiple Myeloma: Insights from Experts at Dana Farber Cancer Institute and Massachusetts General Hospital - Episode 6

Selection and Duration of Therapy in Transplant-Ineligible NDMM

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Expert panelists consider which regimen they would use, and for what duration, in the setting of transplant-ineligible, newly diagnosed multiple myeloma.


Noopur Raje, MD: In myeloma, we are focused on treatment until progression. Andrew, you pointed out that it’s important, especially when you have an overall survival advantage, to use your best drugs up front, specifically in this elderly, more frail patient population. We already have data that the attrition rate as patients go through their first relapse and their second relapse keeps going down substantially. It’s important to use your best drugs up front. Omar, you mentioned when you presented your case that you were thinking RVd [lenalidomide, bortezomib, and dexamethasone] versus dara [daratumumab] and Rd. I see this in clinical practice, when we are talking to oncologists all over, and you sample them, 50% would say, I’m going to do daratumumab-Rd, and the other 50% are going to say, RVd-lite. RVd-lite is something that we all have been a part of. It was initiated at MGH [Massachusetts General Hospital] and Dana-Farber [Cancer Institute], and it’s a 50-patient study. Yet the world has been taken over by RVd-lite. In your patient, it was an easy decision because of the patient having the peripheral neuropathy that you didn’t use RVd. But outside of that, do you ever struggle with the decision of daratumumab-Rd versus RVd, and who are the ones for whom you’d use one versus the other?

Omar Nadeem, MD: That’s a pertinent clinical question that most oncologists are facing when they’re seeing patients like this. As Jacob pointed out earlier, there are great data for both and there is a survival advantage for both. Based on the SWOG study, the RVd was shown to be superior to Rd. Now with the MAIA trial, you have daratumumab, lenalidomide, dexamethasone. There hasn’t been any head-to-head comparison, so we have to have that caveat in place, that we don’t know which one is better. But I think some of the important differences are, one, toxicities. As you pointed out, bortezomib has the issue with peripheral neuropathy, although that’s mitigated now with subcutaneous and weekly use, particularly in the RVd-lite platform. It can still be a problem for the older patients when they develop it. It’s also important to know that in the SWOG study there was fixed duration of bortezomib, whereas in the MAIA trial, we’re continuing daratumumab until progression. Despite fixed duration, you saw a survival advantage with RVd. These are some of the nuances we must keep in mind when we’re choosing. I usually present both options to patients, and I go over the data and look at their comorbidities, and give them an option as to which one they may prefer.

Is there a particular patient for whom I prefer one over the other based on their disease characteristics? I don’t think so. There is some bone involvement benefit with bortezomib, but overall, we’re seeing benefit across the board with the addition of daratumumab to the frontline setting. Most people, as you see with this case, do tolerate daratumumab monthly quite easily. The other thing I see often in practice is when you have a second agent going like that until progression, you have a lot more flexibility. This patient had diarrhea, I was able to dose reduce the lenalidomide and not worry about losing response as much because they’re on another drug. This gives us a lot more flexibility to continue a regimen like that. The practice patterns are shifting more toward daratumumab-Rd as the superior frontline option.

Noopur Raje, MD: The overall survival data, which are so convincing with the daratumumab-Rd data set, is important for everybody to recognize. There are a bunch of studies, Jacob, you mentioned the Alliance [Foundation Trials] effort, which is going to be daratumumab-IRd [ixazomib, lenalidomide, dexamethasone]. That’s a 4-drug combination in this patient population that is being investigated so that it’s not 4 drugs for the transplant eligible, but it’s for all patients. Then there are other efforts wherein people are using daratumumab-RVd-lite because RVd-lite is so well tolerated, and topping RVd-lite with daratumumab will give you the benefits of both RVd-lite as well as daratumumab. These are ongoing trials, we don’t have any data for any of this. But it brings up an important question in this patient population. Your patient was a superstar, and for somebody at his age to do 74 cycles is remarkable. Sure, you dose-reduced lenalidomide, but in real-world practice, somebody in their 80s, the question is, do you treat until progression? Do you end up with a lot of dose modifications? Do you end up dropping one versus the other? What is your practice?

Jacob Laubach, MD, MPP: I tend to continue treatment until progression, provided the patient is tolerating the agent well, and that it’s in line with their preferences. We all have patients in our practices who are in their 80s, and even lower doses of these agents can be challenging to tolerate. If there are tolerability questions, particularly if a patient is in a deep sustained response, it’s reasonable to treat for a certain period of time. I usually prefer a minimum of 18 months of treatment, based on data from the FIRST trial, and would recommend continuation of treatment thereafter. But if a patient strongly prefers having a break from therapy, I might suggest that we closely monitor for a period of time. In some instances, we’re beginning to use MRD [minimal residual disease] to help us with these decisions, but as discussed with the previous patient’s case, I don’t think we’re quite there yet as a field in knowing how precisely to use MRD in that way.

Noopur Raje, MD: Knowing when to stop. MRD, even in this patient population, is being studied. Again, the goal should always be as deep a response [as possible].

Transcript edited for clarity.