Paul Richardson, MD, discusses the safety and efficacy findings from the CC-92480-MM-002 trial of mezigdomide with dexamethasone and daratumumab or elotuzumab in patients with relapsed/refractory multiple myeloma.
Paul Richardson, MD, director of clinical research at the Jerome Lipper Multiple Myeloma Center at Dana-Farber Cancer Institute in Boston, Massachusetts, RJ Corman professor of medicine at Harvard Medical School, discusses the safety and efficacy findings from the CC-92480-MM-002 trial (NCT03989414) which evaluated mezigdomide [CC-92480] with dexamethasone and daratumumab (Darzalex) or elotuzumab (Empliciti) in patients with relapsed/refractory multiple myeloma.
0:09 | In that context, what do we see in terms of treatment-emergent adverse events are summarized here. And in the interest of time, I'll just focus that the non-hematologic grade 3/4 treatment-emergent adverse events were low. Importantly, we did see COVID-19 infection, we did not see mortality, which is an important distinction. We didn't enroll to this study during the pandemic, so this is an important positive in my view. At the same time, most of what we saw was neutropenia.
0:37 | Now, in terms of additional safety data, most important to share with you that most dose-limiting toxicities were due to neutropenia in the first cycle. I think this is an important positive. In terms of efficacy, we are very pleased with it. I'm going to focus first and foremost, on cohort B, which is the mezigdomide/dexamethasone/daratumumab combination. As you can see here, in cohort B3, which has almost 20 patients strong, our response rate approached 89%. In cohort B1, which was the most mature, it was 83%, and the less mature cohort, B2, is currently at 61% and improving. So the combined overall response rate was 78%, which is encouraging in a relapsed/refractory population with a median of at least 3 prior lines.
1:21 | And in that context, if you look at this, you can see the DOR [duration of response] is particularly strong because in this context, you can see that the median DOR has not been reached for B1, not been reached for B2, and the lower boundary here because the data on immature is 9.5. But what's important to note is that the lower boundary here is 23.3 for the B1 cohort. As you'll see in a minute, this bodes well for the durability of disease control that we see. As you can see here in the B1 cohort, we have patients who are 14 and 41 months out on this particular platform, which we think is particularly exciting.
1:57 | Now, how did elotuzumab perform? Well, I think the safety was very clear. In addition, the infection signal was also reassuring, so this was encouraging. In terms of neutropenia, this, again, was the dominant side effect of the .6 mg dosing of mezigdomide. It should be mentioned that .6 and .3 were the 2 doses we explored. What you can see, and that was the same with the daratumumab I should emphasize, but this all proved manageable. Once you move beyond the first cycle. Our response rates for the elotuzumab cohort were a little more modest at 45%. Having said that, .3 and .6 is illustrated here, you can see those clear activity with astringency are in 1 patient and high quality responses elsewhere. But it's fair to say that the duration of response medium currently is 5 with medium follow-up of 7 months. It's important to note these patients were in the main CD38 monoclonal antibody refractory cohort, so an important cohort, but nonetheless, not quite the same striking results as we saw with the CD38 [cohort].