Transcript

I have presented on behalf of my colleagues at EHA 2020 the results of the phase 2, randomized study, EMN10 study, which was a randomized study and enrolled 175 patients who were newly-diagnosed myeloma patients that were non-transplant eligible.

Those patients were randomized into four arms, testing different ixazomib induction combinations -- nine cycles with ixazomib/dexamethasone, ixazomib/dexamethasone plus a third drug which was cyclophosphamide, thalidomide, or bendamustine.

And then for patients completing the induction phase, they proceeded to ixazomib single-agent maintenance for up to two years or intolerance.

We tested different ixazomib combinations believing that this drug in an older population could be a convenient drug since it is oral administration.

What we observed during the induction phase was that adding a third drug to an ixazomib-based combination could increase the overall response rate that was 57 percent with ixazomib/dexamethasone, up to 79, 84% with ixazomib/cyclophosphamide or ixazomib/thalidomide.

The rate of VGPR as well increased from 25 percent with Ixa/Dex to 49 percent with Ixa/Cyclo or Ixa/Thal. And the median progression-free survival was increased as well for the three-drug, ixazomib-based induction from 10.5 months with Ixa/Dex to 12.9 months with Ixa/Thal, and 17.5 months with Ixa/Cyclo, and 22.9 months with ixazomib and bendamustine.

Unfortunately, the primary endpoint of this study was two-year, progression-free survival equal or greater than 65 percent, and this endpoint was not met across all arms because all the two-year, progression-free survival observed with the four combinations were inferior to the 65, predetermined endpoints.

The induction ixazomib was pretty well-tolerated. As a matter of fact, the incidence of all grades, and especially Grade 3 for adverse events was very, very low. Ixazomib was effective in increasing the depth of response obtained by those patients during the induction phase. 50 percent of them increased the depth of response of 10 with ixazomib single-agent maintenance.

The median progression-free survival from the start of ixazomib maintenance was 12.3 months. This confirmed the role of ixazomib maintenance that was also reported in the randomized, Phase 3 study TOURMALINE-MM4 that was just presented at EHA 2020 by Professor Dimopoulos and his colleagues.

What we observed was during the induction phase particularly was that thalidomide was not a good partner for ixazomib as it increased the risk of neuropathy, the risk of dermatological and gastrointestinal adverse events.

And this is probably why, despite the good overall response rate and VGPR rates that did not translate into prolonged, progression-free survival. On the contrary, cyclophosphamide was much better tolerated with a lower rate of treatment discontinuation as with thalidomide.

All in all, we also observed that although cross-comparisons are difficult and always cumbersome, the median progression-free survival of ixazomib/cyclophosphamide and dexamethasone followed by ixazomib was pretty similar to the one reported.

Also, the responses were pretty similar to those reported to BNP in the BSA study, offering a more convenient oral combination regimen. Ixazomib maintenance as well was well-tolerated and that could represent a platform for a more intensive PI-VOS eventually than with lenalidomide, more intensive maintenance. Thanks.