Dr Mark Wildgust: Updated APOLLO Trial Results Confirm Daratumumab Safety in Multiple Myeloma

Subcutaneous daratumumab is well tolerated in patients with multiple myeloma, and adding it to standard-of-care regimens consistently improves outcomes among patients. Updated data from the APOLLO trial bear this out, noted Mark Wildgust, PhD, vice president of Global Medical Affairs/Oncology at Janssen.

Transcript

Given the result of the APOLLO study, what new takeaways do we have about daratumumab in multiple myeloma?

I think in the APOLLO study, we know that those patients who have had an IMiD [immunomodulatory drug] like lenalidomide or a PI [proteasome inhibitor], like Velcade, those patients, their outcomes then can be quite poor. And pom-dex [pomalidomide-dexamethasone] is a common standard-of-care regimen that's used.

So daratumumab plus pom-dex was already approved on a single-arm phase 2 study in the United States. And so the phase 3 APOLLO study really helps us further understand the efficacy and safety of daratumumab when we add it to pom-dex. And we saw a significant improvement in progression-free survival. So, we saw hazard ratio of 0.63. So, that represented a 37% reduction in the reduction of progression or death. And overall, we saw a median progression-free survival of 12.4 months and 6.9 months. So, clinically significant improvements in terms of outcomes.

The other thing with APOLLO is that APOLLO is the first of our phase 3 studies in multiple myeloma that have now read out with subcu dara [subcutaneous daratumumab]. So we have the COLUMBA study before that looked at IV [intravenous] and subcu dara to look at that from a noninferiority perspective. But APOLLO is our first multiple myeloma phase 3 study.

And I think, impressively too, when we look at the safety profile, I think [there is] further confirmation of the safety profile of daratumumab; very, very low rate of infusion-related reactions. It was something like 5% of patients had infusion-related reactions in the APOLLO study, and all of those were grade 1/grade 2. So real confirmation that subcu dara is well tolerated.

We also saw in the APOLLO study an improvement in depth of response. We saw the overall response rate of 69% versus 46%. We also saw a higher VGPR [very good partial response] rate or better, and we also saw a higher rate of MRD [minimal residual disease] negativity. So APOLLO really speaks to what I said before. We now know, and I think we're quite clear, whenever we add daratumumab to a standard-of-care regimen, we always improve those outcomes. And APOLLO speaks to that. And I think the subcu data also confirms how subcu dara is safe. And it's well received, as well.

With follow-up ongoing, will you add data from additional patients?

The phase 3 study is complete. But it's immature. And what we mean is, we really only have just under 17 months of follow-up. And so with a median progression-free survival of 12.5 months, we've got to a point where we have enough events, we know it’s statistically significant. What you will now see with longer follow-up is we'll be able to look at secondary endpoints such as progression-free survival, too, and overall survival. And then we'll be also able to look at further updates in terms of the progression-free survival data itself. I think you’ll basically see longer follow-up giving us more confidence with the results. And a good example for that is here at ASH, we’re reporting the 4-year update from MAIA.

When we originally reported out the 4-year data, we reported out the progression-free survival data from MAIA. We saw the hazard ratio of 0.56, and here now with 4 years’ worth of follow-up, we're seeing a hazard ratio of 0.54. So with longer follow-up, we're really getting that confirmation that that benefit that we saw is stable, is consistent. There's no indication that the APOLLO results will change. But I think most importantly, we'll see that increased confidence of the outcome. We’ll also see, hopefully, the survival results, as well.