Fonseca on First-Line and Second-Line Daratumumab Outcomes for Transplant-Ineligible Myeloma

At 63rd Annual Meeting and Exposition of the American Society of Hematology, CancerNetwork® sat down with Rafael Fonseca, MD, Director of Innovation and Transformational Relationships at Mayo Clinic in Phoenix, Arizona, to talk about an abstract he presented on the use of daratumumab-containing regimens in patients with transplant-ineligible multiple myeloma. He and his fellow researchers found that the first-line MAIA (NCT02252172) trial regimen of daratumumab (Darzalex) plus lenalidomide (Revlimid) and dexamethasone (D-Rd) was superior to lenalidomide, bortezomib (Velcade) and dexamethasone (RVd) this was originally verified in the SWOG S0777 trial (NCT00644228).


Our simulation went as follows. We decided to watch SWOG [S0777] in those over 65. Again, as published, there is no difference in overall survival [compared with the MAIA trial]. But because it has a mixed population, we looked at a real-world dataset of patients who would receive first-line treatment with RVd in that older population, so that was number one. By the way, we did a study with SWOG and the results are the same. We also took the data on D-Rd that was published in MAIA, both for the D-Rd arm and the Rd arm – so you have their D-Rd, RVd and Rd, those are the 3 diets that we let’s study for first-line therapy.

The second point is that we asked you if you were treated with D-Rd, what would you use for that first relapse? We assume it would be mainly carfilzomib [Kyprolis] and pomalidomide [Pomalyst]– diets containing. Whereas if you were treated with RVd first or with Rd alone, you would be treated with a regimen containing daratumumab. So that would be the second line. And for that information, we’re using the Flatiron Health database to see what we’re seeing in terms of treatment duration and overall survival. So these are the 2 sets of data.

Now we’ve looked at the attrition range. Our group and the work of others have shown that there is significant attrition between different lines of treatment, especially for patients who are not eligible for a transplant. We have published that this attrition can reach 50%. Now we looked at an upper limit and a lower limit, and I’m going to focus on the results of those who have this lower limit which was 27.2%. But regardless, the results are the same no matter what attrition rate we use.

A logical question would be, ‘why wouldn’t you use something like the POLLUX essay [NCT02076009] as a witness for this first relapse? The reason is that patients in politics are different from patients who would enter [the MAIA trial]. Two descriptors that would justify this are: first, they are about 10 years younger. And as another example, about 60% of them had already undergone a stem cell transplant, so it’s not the same patient population. We also use the real world datasets for second line data.

And we took the 3 states, of course, being the first line, the second line, and unfortunately the patients who succumb to the disease. What we found was that the overall survival for patients who started on D-Rd and then were followed by pomalidomide and carfilzomib would be about 9.1 years, or about 2.5 years longer than at the beginning of the RVd. That’s almost 3.5 years longer than if you start with Rd alone. Now I think we all understand. If you think about it, everyone understands. If we had a prospective randomized trial that could look at all of this with continuation of treatment for these patients, including intention to treat and attrition, that would be ideal. But given that we have 2 diets that are accepted, we thought it was quite useful to make this comparison. Our results suggest that it makes sense to start with the best drugs at the beginning, the best drug in this case being the MAIA regimen. The fact that you have a diet that will not produce peripheral neuropathy is critical, especially as patients live, 5, 10, and 15 years [longer], where it will have a significant impact on their quality of life.


Fonesca R, Facon T, Hashim M, et al. First-line use of daratumumab, lenalidomide, and dexamethasone confers a survival advantage over second-line use of daratumumab-based regimens in transplant-ineligible patients with multiple myeloma : analysis of different clinical scenarios. Presented at the 2021 Annual Meeting of the American Society of Hematology. December 11-14, 2021. Virtual. Summary 118.

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